Compositions for cleaning and decontamination

ABSTRACT

Provided among other things is a cleaning composition comprising: a carrier fluid; and Minute Fibrils suspended in the carrier fluid, wherein the composition is protein cleaning effective.

This patent application claims the benefit of Provisional PatentApplication U.S. Ser. No. 62/402,394, filed Sep. 30, 2016, including itsappendix, and Provisional Patent Application U.S. Ser. No. 62/563,975,filed Sep. 27, 2017 (NOVA003P2), including its appendices, all of whichare incorporated herein by reference in its entirety.

Embodiments of the invention pertain to compositions, methods andapparatus for the decontamination, cleaning, sanitization, disinfection,sterilization, storing in disinfected or sterilized condition, andtreatment, of long narrow lumens, channels and tubes such as inendoscopes, other luminal medical devices as well as other surfacesirrespective of geometries or material of construction.

Though the invention is applicable to many fields, the field thatprimarily engendered the current invention is the field of cleaning andsterilizing endoscopes, and the long narrow channels found in thesedevices. Infections traced to endoscopes have been a tremendous problem,yet the mechanical complexity of the devices means that it has beenimpractical to utilize single use devices, and even the componentscannot at this time be switched out with single use components. Theconstruction and heat-sensitive materials of flexible endoscopesgenerally preclude the use of high temperature steam for sterilization,and the long length and the small cross-sectional size of the variousinternal tubing channels cause fundamental difficulty in cleaning,disinfecting, and sterilizing these channels. While there are manyexamples of serious infection reported, a particularly serious reportwas of two patient deaths at the UCLA Medical Center in 2015 fromcarbapenem-resistant Enterobacteriaceae (CRE) infection transmitted bycontaminated duodenoscopes, namely Endoscopic RetrogradeCholangiopancreatography (ERCP) Duodenoscopes. CRE contamination hasbeen linked to biofilm growth in ERCP endoscopes, and this biofilm canbe related to inability to clean the internal channels of the endoscopeor other parts of the elevator section of the endoscope.

Biofilms are highly resistant to standard cleaning, and a common causeof infectious diseases, especially from medical devices. Biofilms adhereon surfaces utilizing layers of extracellular polysaccharide substances(EPS) in which the microorganisms are embedded. EPS provide biofilmstructural stability and also protection from environmental factors suchas antimicrobial substances. Though organisms may be dormant in abiofilm, the biofilm will release bacteria in the more infectiousplanktonic form.

The suction and biopsy channel (“SB channel”) most consistently contactswith materials that create a risk of infection, and the growth ofbiofilm It also typically has an inner diameter (e.g., >2.8 mm such as3.2 mm or 3.7 mm) that allows for more vigorous cleaning, includingscrubbing with a brush. Yet, Applicant has found that standard protocolsdo not remove biofilm, and especially does not remove build-up biofilm(BBF, described further below). FIGS. 1A and 1B show scanning electronmicroscope images (SEMs) of an SB channel lumen after manual brushingfive times according to a standard protocol. The SEMs show build upbiofilm strips that are not removed by manual brushing. Despite extendedbrushing, biofilm removal from the channel lumen is incomplete. FIG. 1Bis at higher magnification, such that the outlines of the bacteria canbe seen.

Further a typical endoscope has additional, narrower channels, such asair, water, irrigation, forced jet and elevator channels. These channelscan have for example an ID of 1.5 mm or less. These channels are notimmune to acquiring biological contamination, including contaminationmigrating from other parts of the endoscope. These channels cannot beconventionally brushed. Given the strong limitations on tools forcleaning these channels, they represent a major source of concern forspreading infection.

Beyond the narrow width of SB and narrower channels, another challengeis that the material used, most frequently Teflon®, is resistant towetting with aqueous fluids, making it more likely that patches ofmaterial are not effectively contacted with cleaning fluids (such asrinse agents, cleaners, disinfectants, sterilants, enzyme solutions, andthe like). This lack of wetting can also affect high-level disinfectantssuch as glutaraldehyde, hydrogen peroxide, ortho-phthalaldehyde,peracetic acid, and the like. The narrow width of these channels, andthe pressure limits on their operation, mean that the hydrodynamicdetachment force (HDF) that can be generated by conventional flow islimited.

After traditional cleaning and disinfecting, the endoscope is typicallyflushed with alcohol, and purged with air to dry the interior channels.However, publications by Cori L. Ofstead and co-authors have shown thatpockets of moisture remain, which promotes biofilm formation.

One aspect of the current invention was the realization that gels orother high viscosity fluids pumped through these channels at pressuresfalling within the operating parameters for an endoscope (e.g., 28 psi)can provide shear stress on the surfaces of the channels higher thanthat of conventional water-based cleaners to more effectively removecontaminants. Applicant has shown this base invention to be effective inimproving the removal of bacteria and organic soil (protein, lipids,carbohydrate, hemoglobin or similar substances) from the channels.Without more, it is less effective in removing BBF.

What Applicant discovered was very effective in removing biofilm andeven BBF were compositions (not necessarily gels) containing fibrillatedpolymers. These are polymers with thicker (often crystalline orsemi-creystalline) polymer bundle segments, from which branch thinnerpolymer bundle segments. With cellulosic fibrillated polymers, there maybe three tiers of polymer bundles, as well as polymer single chains.Without being bound by theory, it is believed that as this type ofpolymer moves across the surface to be cleaned in a network, the stiffercomponents are periodically shifted to collide and interact with thesurface, or to cause segments of branched polymer bundles to so collide,providing localized shear stress that provides contaminant-dislodgingforce. The localized shear stress periodically applied is believed to befar higher than the bulk shear stress. The network of fibrillatedmaterial provides thousands of such contacts to any narrow area, andalso provides a network for entrapping and carrying the contaminants outof the channels.

SUMMARY

Embodiments of the disclosure comprise a cleaning and storagecompositions, methods of use, devices utilizing, and the like,substantially as shown in and/or described in connection with at leastone of the figures, as set forth more completely in the claims. Variousadvantages, aspects and novel features according to embodiments of thedisclosure, as well as details of an illustrated embodiment(s) thereof,will be more fully understood from the following description anddrawings.

DESCRIPTION OF THE DRAWINGS

So that the manner in which the above recited features of the presentinvention can be understood in detail, a more particular description ofthe invention, briefly summarized above, may be had by reference toembodiments, some of which are illustrated in the appended drawings. Itis to be noted, however, that the appended drawings illustrate onlyillustrative embodiments of this invention and are therefore not to beconsidered limiting of its scope, for the invention may admit to otherequally effective embodiments.

FIGS. 1A (see 500 micron bar) and 1B (see 10 micron bar) depict abiofilm remaining after traditional cleaning;

FIG. 2 shows a schematic of the structure of cellulose fibril bundles;

FIG. 3 shows shear thinning behavior during dynamic viscositymeasurements;

FIG. 4 shows pressure vs. flow rate for a narrow channel;

FIG. 5A (see 100 micron bar) shows biofilm in a channel by SEM;

FIG. 5B (see 500 micron bar) shows biofilm removal in a channel withMinute Fibrils;

FIG. 5C (see 500 micron bar) shows incomplete biofilm removal withconventional cleaning;

FIGS. 6A (see 10 micron bar) and 6B (see 500 micron bar) show anexemplary structure of a Minute Fibril composition as visualized by SEM,specifically 1.4% w/w Exilva Forte in Modified CS19 (carrier fluiddescribed below);

FIG. 7 (see 2 micron bar) shows a portion of Minute Fibril material withentrapped biofilm material, as imaged by SEM after use in cleaning thebiofilm from a channel;

FIG. 8 shows an apparatus and method for cleaning an open surface;

FIG. 9 shows another apparatus and method for cleaning an open surface;

FIGS. 10 (oblique view), 11 (side view) and 12 (top, cut-away view) showanother apparatus and method for cleaning an open surface; and

FIG. 13 show a further apparatus and method for cleaning an opensurface.

To facilitate understanding, identical reference numerals have beenused, where possible, to designate comparable elements that are commonto the figures. The figures are not drawn to scale and may be simplifiedfor clarity. It is contemplated that elements and features of oneembodiment may be beneficially incorporated in other embodiments withoutfurther recitation.

DETAILED DESCRIPTION

Minute Fibrils—General

“Minute Fibrils” (MFs) is a term coined to encompass what the industryterms as microfibrillated cellulose and nanofibrillated cellulose (whichare basically the same thing) and substantially equivalent structuresmade from synthetic polymers, including without limitation those made bythe Lyocell melt spinning process or similar processes. The structure ofcellulose is illustrated in FIG. 2 (adapted fromnutrition.jbpub.com/resources/chemistryreview9.cfm). The structure ofmicrofibrillated cellulose can be discussed with reference to thisfigure. In native cellulose structures there are native cellulose fibers(diameter=about 20,000 nm to about 60,000 nm), smaller macro fibrilbundles and still smaller micro fibril bundles. There are believed alsoto be single polymer chains (which do not visualize as easily inmicroscopy). Microfibrillated cellulose is cellulose that has typicallybeen treated mechanically, chemically, enzymatically, or withcombination treatments to separate out macro fibril bundles and microfibril bundles. These can loop off larger fibril bundles, or extend fromlarger fibril bundles. It may be that there are unconnected micro fibrilbundles, but the amounts are believed to be small, and the fibrilbundles are believed to associate with the connected fibril bundles.There can be two or more tiers of diameter sizes. What is important isthat the micro fibril bundles (or their analog) are connected tostiffer, larger bundles.

A useful measurement parameter for Minute Fibrils is the hydrodynamicsize (HDS), especially the mean HDS (MHDS). This is measured by laserdiffraction of a highly dilute suspension, using a Mastersizer 3000(Malvern Instruments), [José et al., On the morphology of cellulosenanofibrils obtained by TEMPO-mediated oxidation and mechanicaltreatment, Micron, 72, 28-33 (2015)]. Though energy is applied (bysonication) to separate structures, it is not clear whether the entitymeasured is a single structure, or a floc of two or more. The substanceso measured is a “fibrillated entity.”

It has been found that microfibrillated cellulose that has beenprocessed to the extent that the MHDS is as low as about 20 micron(micrometer) is less effective, if provided on its own, thanmicrofibrillated cellulose with MHDS of for example 30 to 70 micron.Surprisingly the larger microfibrillated cellulose is in someembodiments even more effective if appropriately mixed with smallermicrofibrillated cellulose. These and all other lessons drawn fromcellulose are expected to be applicable to synthetic Minute Fibrils aswell. Thus, in embodiments, it is useful to mix a Minute Fibrilcomposition having one MHDS with one having a MHDS of 50% or less. Inembodiments, a ratio having more of the larger Minute Fibril component(by dry weight) is used, such as a ratio of about 1.5:1 or more, such asabout 2:1 or more, or about 3:1. In embodiments, the distribution of thesource compositions is tight enough such that the mixture is indicatedin the product by a bimodal (or for further mixtures, multi-modal)distribution.

In embodiments, the Minute Fibrils comprise relatively large diameterfibrils, which can be expected to provide stiffness, which can be termed“Type B” Fibrils, for example having diameter from about 100 nm to about20,000 nm (20 micron). They can further comprise “Type A” fibrils of asmall diameter range, e.g., 10 to 90 nm. SEM images show Type A fibrilsconnected to Type B fibrils. This is not to say that all Type A fibrilsextend from Type B fibrils.

Type A fibrils are also referred to herein a “nanofibrils.” These arebelieved to be more involved in entangling fibrillated entities.

For cleaning narrow channels (e.g. SB channels or narrower), the lengthof the starting fiber bundle can be important. Length can be difficultto measure after the fiber bundle has been processed to Minute Fibrils.Favorably the number average length is about 1000 microns or less, orabout 800 microns or less, or about 500 microns or less. “Narrowchannels” are channels or tubes with ID of about [6 mm] or less, andsufficient length that cleaning with brush is not practical or tends tobe ineffective against BBF, such as outlined herein for SB channels.

For cleaning, typically, a “fibrillated network” is used. A fibrillatednetwork is a 3-D network structure made from the interaction offibrillated entities as the result of entanglements of fibrils as wellas due to hydrogen bonding (or other non-covalent bonding mechanismsincluding electrostatic) when the fibrillated materials are properlymixed with water or solvents.

Without being bound by theory, it is believed that when a suspension,dispersion, network or mixture of Minute Fibrils flows in channel or thelike, the fibers, fibrils or their flocs (aggregates that move andtumble as a unit) or their nano-structures as described herein contactor nearly contact the surface of the channel or tube during flow,resulting in scraping, abrading, removing, detaching, desorbing oreffecting localized brushing-like action at a very small size scale.These cleaning processes occur when the gel-like network structure suchas Minute Fibrils moves past the wall while the gel structure such asMinute Fibrils are in contact or nearly in contact with the wall. Thisaction is believed to repeatedly create localized high hydrodynamicdetachment force or even make direct contact with the surface beingcleaned, with that force or stress being sufficient to detach, desorband remove contaminants.

The very large specific surface area of the Minute Fibrils cansignificantly facilitate material transfer and removal of contaminantsfrom the walls of channels, tubes or confined space during flow. Thespecific surface area of for example some nano- or microfibrillatedcellulose material can be more than about 10 m̂2/g and up to more than300 m̂2/g and in some cases can be more than one or two billion m̂2/g,which can produce effective and efficient treatment and can clean wallsas they contact or nearly contact them during flow. The large surfacearea can facilitate adsorption of contaminants and can trap contaminantfragments during cleaning. The surface area can be estimated from SEMmicrographs, adsorption of nitrogen or other gas, surfactant or othermolecular probe with known surface area or combination of methods as itis known in the colloid and surface science or materials scienceliterature.

For the purposes of the claims, measurement is by the adsorption ofnitrogen onto the surface of the material. This technique is based onthe Brunauer-Emmett-Teller (BET) theory of the adsorption of gasmolecules on a solid surface. In this technique, the material isprepared by first desorbing whatever is adsorbed onto the surface of thematerial, and then the material is placed in an environment where it canadsorb nitrogen. The amount of gas adsorbed at a given pressureindicates the specific surface area of the material. This measurement ofthe amount of the amount of adsorbed gas can be made by measuring thechange in the amount of gas present, or by measuring the change in theweight of the material.

In certain embodiments, the specific surface area for the Minute Fibrilcomposition providing the major portion (50% or more) of Minute Fibrilsis about 30 m̂2/g to about 300 m̂2/g, or higher in some cases.

A composition has a protein cleaning effective amount of fibrils plusany gel-forming polymer or any stiffening components if that amount,formulated at one or more of pH 7 or 9 in CS-19 (described below) wouldclean Austrian Soil-derived protein (applied as described below) fromthe inner surface of six foot length of 3.2 mm ID PTFE tubing to reduceadherent protein by 50-fold or more to a level of about 6.4 μg/cm2 orless.

A BBF cleaning effective amount of fibrils plus any gel-forming polymeror any stiffening components is one that if that amount, formulated atone or more of pH 7 or 9 in CS-19, would remove BBF (formed as describedbelow) from the inner surface of six foot length of 3.2 mm ID PTFEtubing as measured by SEM analysis.

A composition (for any gel, fiber or other cleaning embodiment) isprotein cleaning effective if it cleans Austrian Soil-derived protein(applied as described below) from the inner surface of six foot lengthof 3.2 mm ID PTFE tubing to reduce adherent protein by 50-fold or moreto a level of about 6.4 μg/cm2 or less.

A composition (for any gel, fiber or other cleaning embodiment) is BBFcleaning effective if it removes 90% or more of BBF from the innersurface of six foot length of 3.2 mm ID PTFE tubing as measured by SEManalysis.

For formulations configured for open surfaces and having too muchviscosity for measuring protein or BBF removal in a tube, ifformulations included within the components are protein cleaning or BFFcleaning, the formulation is so effective.

Useful concentrations of Minute Fibrils can include for example fromabout 0.2% w/w to about 4% w/w. The amount can vary with the specificcharacteristics of the Minute Fibrils and the carrier fluid. Forexample, with one Exilva (described below) Minute Fibril composition,1.2% by weight was not sufficient to erode and remove BBF in 20 minutes,while compositions containing 1.4% or 1.7% or 1.9% could erode andremove BBF in about 5 to 10 minutes.

In certain embodiments, flocs of the Minute Fibrils have a mean diameterof about 50 to about 100 microns

Cellulosic Minute Fibrils—Production

Methods of production of Minute Fibrils include mechanical processing,TEMPO-catalyzed processing, and enzymatic processes, and combinations ofthereof. Exilva grade microfibrillated cellulose (made by Borregaard) ismade by a purely mechanical process with many passes throughBorregaard's processor machine, which includes a form of microfluidizer.The Lyocell process, which can be used with cellulose, is similar towhat is used in making Nylon and it can also be used with acrylics orother polymers. TEMPO (a common name for a catalyst whose chemical nameis (2,2,6,6-Tetramethylpiperidin-1-yl)oxyl or(2,2,6,6-tetramethylpiperidin-1-yl)oxidanyl) is used in some processesto induce partial cleavage in the cellulose. Sodium hypochlorite orsodium bromide can also be used as oxidizing agents (for example alongwith TEMPO) for cleavage, in combination with mechanical force. Avariety of mechanical processes can be used such as high pressurehomogenization, microfluidization, grinding, refinery-based processes,cryocrushing, and high intensity ultrasonication. It can includedirecting jets of fiber-containing liquid to impinge on one another. Aprocess may use for example, two passes through a grinder or refiner,and multiple passes through a homogenizer.

Materials made by Borregaard have subclassifications including:

TABLE 1 Sub-Grade Mean Hydrodynamic size Size Range Exilva Forte ~20micron ~1 to ~1000 micron Exilva Piano (various ~36 to ~60 micron ~1 to~1000 micron grades) Exilva Piano Light ~70 micron ~1 to ~1000 micronSensifi (in admixture ~100 micron ~1 to ~1000 micron with CMC)

As analyzed by numerous SEMs at several magnifications, someillustrative cellulosic Minute Fibrils have the following features:

TABLE 2 Microfibrillated Fibers (Type B) Fibrils (Type A) CelluloseDiameter Length Diameter Length Exilva Forte  0.5-3 μm 10-100 μm 30-60nm  >2 μm Exilva Piano 0.1-20 μm  5-150 μm 50-70 nm 2-3 μm Exilva Piano0.3-20 μm 20-200 μm 20-75 nm 1-5 μm Light Sensefi 0.25-15 μm   5-60 μm30-60 nm 0.4-1.0 μm   

The results of Table 2 include a summary of the SEM analysis of some ofthe fibrillated materials as described in embodiments of the invention.The top three materials listed in the Table represent different degreesof fibrillation and are sold without other additives. The fourthmaterial (Sensefi) is made by a special process and as sold includescarboxymethyl cellulose (CMC). The fibrillated material, made as dilutesuspension, was deposited to SEM stubs and coated according to acceptedSEM imaging methods. The data is divided based on manual image analysiswhere fibers and fibrils are listed separately. Diameter and length offibers and fibrils are includes as seen in the micrographs. The rangesof diameter and length of fibers and fibrils include the most prevalentsizes. At least 1000 fibers and 1000 fibrils were examined for each ofthe four materials. Diameters can be highly accurate since they can beobtained from the micrographs. On the other hand, the lengths can beless precise since it difficult to ascertain because of highmagnification of the SEM images. The SEMs for each material was obtainedat 100×, 1,000×, 2,000×, 10,000×, 50,000× and 10,0000×. In an embodimentof the invention, the diameter and length of the fibers and fibrilsrepresent the ranges used to prepare the networks described in thespecification. This can be important since the diameter and length arebelieved to contribute to the mechanical properties of the network,especially strength, stiffens and rigidity which are important forcleaning according to the invention. Although SEMs provide specific dataabout the morphology of the fibrillated materials, other definitions ofthe fibrillated materials can be obtained from laser scattering resultsof the equivalent hydrodynamic volume as described elsewhere herein.Additional description of the fibrillated materials include viscositydata and rheological date when suspended in liquid as describedelsewhere herein.

Microfibrillated fibrous materials are now commercially available fromsuch suppliers as: Borregaard (Sarpsborg, Norway) (products includeExilva, Sensefi); Wiedmann Fiber Technology (Rapperswil SG, Switzerland)(WMFC_QAdvanced); Engineered Fibers Technology LLC (Shelton, Conn.)(EFTec™ nanofibrillated fibers); American Process, Inc. (Atlanta, Ga.)(BioPlus® Fibrils); Celluforce (Montreal, Canada); Forest ProductsLaboratory (US Department of Agriculture); Lenzig AG (Austria)(productsinclude Lyocell); Weyerhaeuser (Seattle, Wash.)(products includeLyocell); and other suppliers in Scandinavia and Japan.

Synthetic Minute Fibrils—Production

Synthetic polymers can be formed into macro fibril structures forexample by spinning (extruding) a solubilized formulation. For example,cellulosic polymers can be so extruded, for example usingN-methyl-morpholin-N-oxide (NMMO) as the solubilizing solvent. Othersolvents can be chosen as appropriate for solubilizing the polymer inquestion, such as acrylics and others. The spun fiber can then be cutand mechanically converted into a Minute Fibril form as outlined above.For example, Engineered Fibers Technology (Shelton, Conn.) sellsfibrillated polymers of Acrylic (CFF®, acrylic copolymer), Lyocell(Tencel®, for wood pulp), LCP (Vectran®, aromatic polyester), PBO(Zylon®, crystalline polyoxazole), Para-aramid and Cellulose (wood andnon-wood).

Gels for Cleaning

A gel is a deformable material or a fluid-like composition. For use incleaning long narrow channels a gel should have a yield shear stressabove which it starts to flow. A gel typically comprises a network ofentangled macromolecules, fibers or fibrils, or crowded swollen microgelparticles. For applied shear that is less than the yield shear stress,the gel does not flow at all or the gel can move as a single body orintact network as long as the network is not destroyed during act ofmovement. For applied shear stress that is above the yield shear stress,the gel flows as the network is destroyed or partially destroyed. Theyield shear stress behavior can be a result of a network structurewithin the gel, which to some degree breaks apart when yielding occurs.A gel can also be non-Newtonian, such as shear-thinning, as adescription of its rheological flow properties for flow that occursbeyond the yield point at which the gel begins to flow. A composition ofMinute Fibrils can have these properties.

Gels can be made from hydropolymers polymers such as Carbopols (highmolecular weight, polyacrylic acid polymers). Carbopols or carbomers aresold commercially under the name Carbopol®, by the Lubrizol Corporation,Wickliffe, Ohio. These polymers may be cross-linked and insoluble inwater although they do not have to be cross-linked. A network structureof these gels can be seen in cryo-sections visualized by a ScanningElectron Microscope. This is further described in: Rheologicalproperties and microstructures of Carbopol gel network system, byJong-Yun Kim et al., Colloid and Polymer Science, July 2003, Volume 281,Issue 7, pp 614-623. Even at about 0.1 or 0.2% concentration by weightin water, a fibrous three-dimensional gel network system forms. Asvisualized, the network can show fractal aggregates. In embodiments, thegel utilized shows such fractal aggregates. As the amount of polymerincreases, the strings or structures or swollen particles of the fibrousnetwork become thicker and form honeycomb-like structures which canpossess a yield shear stress.

As explained in a data sheet for Carbopol® polymer, the polymer can beeither soluble or insoluble in water. If the polymer is linear ratherthan crosslinked, the primary particle would be a collection of linearpolymer chains, intertwined but not chemically bonded via covalentbonding. A linear polymer form of Carbopol® is commercially available asCarbopol 907 and it is soluble in water. In contrast, crosslinkedpolymers generally do not dissolve in water, and can be termed“water-insoluble.” All Carbopol® polymers other than Carbopol 907 arecrosslinked, and are water-insoluble. Polyacrylic acid polymers brandedPemulen®, and Noveon® are also insoluble. These polymers swell in waterup to 1000 times their original volume (representing ten times theiroriginal diameter) to form a gel when they are exposed to a pHenvironment above 4-6. The form of Carbopol® polymer exemplified hereinhas a Molecular Weight of 3-6×10̂6 Daltons, with the primary particleshaving a dimension of 20-70 nm in diameter. The primary particles inturn are believed to form secondary aggregates having a typical size ofthe order of 0.2 μm. The secondary aggregates in turn are believed formtertiary aggregates having a typical size range of the order of 0.2-2μm. A process for forming the composition of Carbopol used herein canstart with wetting Carbopol in water to form a dispersion. This can bedone with water, and the resulting suspensions can for example have a pHin the range of approximately 3 to 4, and in this situation thedispersion has a relatively low viscosity, which can be close to theviscosity of water. After this dispersion is subjected to neutralizationwith Triethanolamine or an alkali such as sodium hydroxide or potassiumhydroxide, which raises the pH ˜8, the particles swell to approximately1000 times their original volume, which produces a fluid that has highviscosity and high yield shear stress. The resulting viscosity can be2,000 to 10,000 cP (centipoise) at Carbopol® concentrations of 0.2% to0.3%, for the shear rates typically used herein. Thus, the structure andproperties of Carbopol in water are significantly responsive to chemicalproperties of the carrier fluid, such as the pH of the carrier fluid.

Such carbopol gels have been shown to have a yield shear stress thatmakes it feasible to pump them through the channels of an endoscope.Their shear thinning properties assist in such pumping through channels.

Carbopol is not the only substance that forms gel structures in water.Examples of other substances that exhibit such behavior includepolyacryamides, other synthetic polymers, cellulosics, and many naturalpolymers of plant, animal, or sea origins including weeds and algae.Some of useful gels can exhibit yield shear stress and others may nothave yield shear stress but still can be effective in cleaning a goodrange of contaminants weaker than BBF

Useful concentrations of gel-forming polymer can be for example fromabout 0.05% w/w to about 2% or 3% w/w.

A gel of this type can be used in combination with Minute Fibrils.

Gel-Minute Fibril Combinations

Given combinations where the concentration of the non-MF gel-formingsubstance does not by itself produce a gel, and the concentration of theMinute Fibrils does not by itself produce a gel; it has been found thatthe combination of the concentration of the together can produce a gelor network. Other such combinations can also be useful. It has beenfound that such combination formulations produce a cleaning effects whenfor example flows through a tube or passageway. It is believed, althoughit is not wished to be limited to this explanation, that a formulationcomprising a non-MF gel-forming substance and Minute Fibrils can haveless of a tendency to clog a passageway or to leave Minute Fibrilsbehind in the passageway, as compared to a gel of similar properties orsimilar cleaning effectiveness that is formed by the presence of MinuteFibrils without the additional presence of a non-MF gel-formingsubstance. This is advantageous because a clog, especially a clog thatresults from fibers alone, could require additional steps to unclog, orit might even be impossible to unclog. A clog could require expensiverepairs to an endoscope or could even be impossible to repair. Water orliquid vehicle including cleaning ingredients can be used to form thecomposite gel according to embodiments of the invention.

In an embodiment, the yield shear stress of a Minute Fibril network canbe increased by incorporating a gel-forming substance like Carbopol thatpossesses high yield shear stress by itself It is known that somecross-linked carbopol gels can have high yield shear stress more than100 Pa when made at pH about 7.0 to 9.0. On the other hand, some MinuteFibril networks can have low yield shear stress values, for examplebetween 1 to 60 or 100 Pa. Accordingly, a composition comprising a ratioof Minute Fibrils and carbopol (or other yield shear stress formingsubstance) can produce a stronger network with high composite yieldshear stress. This composite network can possess higher strength than anetwork made with Minute Fibrils only. As described elsewhere herein anetwork composition with higher strength can be advantageous withrespect to cleaning tenacious contaminants such as build up biofilm Theproportion of Minute Fibrils and the yield shear stress contributingsubstance can be adjusted so that effective cleaning can be obtained.

In an embodiment, inclusion of a small concentration of an ionic polymersuch as carboxymethyl cellulose (as exemplified by one having molecularweight more than 250,000 and 80% substitution at about 100 to 200 ppm byweight) in the Minute Fibril composition can aid in cleaning BBF.Without being bound by theory, the small concentration of suchcharge-providing material is believed to disperse the fibrils due toelectrostatic repulsion and make them extend so that they canparticipate in producing more entanglement, which leads to making astronger network. This discovery can be extended to using cationicpolymers if positive electrostatic charge is desired. The amount ofpolymer is judiciously added to avoid creating weaker networks orlubrication of the network-surface boundary.

Analytical BBF

A standard protocol has been used to produce a BBF for testing thecompositions of the invention. This protocol, described in detail inExample 2, involves one week of growth including applications ofglutaraldehyde at defined times during that week as documented by Alfaet al. [Reference: A novel PTFE-channel model, which simulates lowlevels of culturable bacteria in build-up biofilm after repeatedendoscope reprocessing. Alfa et al., Gastrointestinal Endoscopy 85(5),Supplement, pp. AB67-AB68, 2017].

Stiffening or Abrasive Components

Additional components can be added to provide a stiff network, which canbe useful to supplement the effects of the stiff components of MinuteFibrils, or provide abrasives to Minute Fibrils or gels. Non-polymerabrasives can also be added. The manner in which these components areadded can have a notable effect. Without being bound by theory, ifintroduced with high energy, they are anticipated to uniformlydistribute. If added with less energy, e.g., whisking, they areanticipated to more strongly populate the outer parts of flocs of MinuteFibrils. In certain embodiments, such as for example cleaning opticallenses, extra care may be taken with the selection these components toavoid damage. In certain embodiments, such as cleaning or sharpeningblades, the selection of these components may be made to accentuatemicroabrasion.

Stiffening Polymers

Stiffening polymers are exemplified by microcrystalline cellulose (MCC),though other polymers that can provide this function can be substituted.MCC is available in various grades from several sources and vendors, andcan be obtained from FMC Corporation, Newark, DE, under the nameAvicel®. Microcrystalline Cellulose is made by a hydrolysis processwhich removes the amorphous fraction from cellulose fibers and controlsthe degree of polymerization at the same time. In embodiments, MCCfibers are not as elongated (as described by length/diameter ratio) assome of the Minute Fibrils described herein. Microcrystalline Celluloseis safe and is used extensively to make tablets and other pharmaceuticaland food products.

Microcrystalline Cellulose can form gels that have increased viscositywhen standing, especially when the Microcrystalline Cellulose isco-processed with carboxymethyl cellulose (CMC) polymer. Because of itselongated shape and stiff crystalline nature, Microcrystalline Cellulosedoes not readily form gels that have entangled network structures;however, it can make some kind of 3D network that forms weak gels overone or more weeks. Accordingly, gels based on MCC-CMC may be weaker (interms of yield shear stress) compared to gels made from Minute Fibrils.

Because of its crystalline nature, MCC can provide rigidity, stiffnessand hardness to the Minute fibril compositions described herein. Inaddition, when MCC is included as a component of the Minute Fibrilnetwork at sufficient concentration, from about 0.1 to 10% by weight andpreferably at about 1 to 3% by weight of the Minute Fibril composition,it can provide a stronger network (or increase yield shear stress andstorage modulus) and abrading action at the wall or surface to removestrong contaminants such as for example build up biofilm.

If added with high energy, the effect of MCC on improving BBF cleaningis less than if added to a Minute Fibril network with lower energy.

Solid Particles

In yet another embodiment of the invention, the composition may compriseMinute Fibrils (or gel) and also solid particles. In embodiments, thehardness of fluid Minute Fibril network compositions can be increased byincluding solid particles at suitable concentration from 0.1 to 5% andpreferably from 0.2 to 3% by weight of the Minute Fibril composition.Accordingly, Minute Fibril compositions including solid particles orfibers are effective in removing biofilms and contaminants frompassageways and surfaces.

Hardness can be described, at least qualitatively, using the Mohshardness scale that was originally developed in the field of mineralogy,or another scale. It is believed that the hardness of cellulose is about3 on the Mohs hardness scale. As an example, the particles may be simpleinorganic substances, which may be insoluble or poorly-soluble in water.For example, Calcium Carbonate (CaCO3) is one such substance. Calciumcarbonate is believed to have a Mohs hardness of around 4. Colloidalsilica (silica gel) is another possible substance. Colloidal silica isnot as hard as ordinary silica or quartz. The Mohs hardness of silicagel is around 4, similar to that of CaCO3. Silica gel is amorphous andis not very scratchy. Ordinary silica or quartz, in contrast tocolloidal silica, is hard enough to remove biofilm, but also is hardenough to scratch typical polymeric materials used for the wall of thepassageway. Quartz, which is ordinary silica, like sand, has a Mohshardness of 7. Silica gel is FDA approved for use as a dentifrice alsois approved for exfoliating, and it does not cause silicosis.

Another suitable particle material of the inventive composition couldinclude crushed olive pits and crushed cashew nut, both of which areavailable commercially in a range of particle size from 50 microns tomore than 500 microns. Such material can be mixed in with othercomponents of the Minute Fibril composition. Particles or fibers usedcan include: Wool made by Goonvean, Nylon made by Goonvean, Olive Stonemade by Goonvean, Syloid EXF150 (SiO2) made by W. R. Grace, FMC LatticeNTC-80 Microcrystalline Cellulose, FMC Lattice NTC-61 MicrocrystallineCellulose, FMC NT-100, FMC NT-200, Precipitated CaCO3, and the like.

Insoluble or poorly-soluble material can also be formed within thecomposition by a precipitation reaction that could take place upon themixing of appropriate aqueous-solution ingredients. Examples include butnot are limited to precipitated calcium carbonate, silica, calciumphosphates including hydroxyapatite, fluorophosphates, alumina and othermaterials. The particles formed within the network can be crystalline,amorphous or comprising mixed phases as desired. The particle size andsize distribution of particles formed within the network can for examplerange from 50 nanometers to several microns possibly in the range from0.5 to 100 microns, or even up to 500 microns or more. For example, areaction that produces insoluble calcium carbonate particles within thenetwork includes mixing calcium chloride and sodium carbonate which canbe formed in situ within the Minute Fibril network during preparation.Other reactions include: reaction between various carbonates (e.g.sodium carbonate) and calcium hydroxide; reaction of soluble calciumsalt and carbon dioxide gas; reaction between ammonium carbonate andcalcium hydroxide or other reactions known to form calcium carbonate asis known in inorganic chemistry. The sizes of such produced precipitateparticles can be dependent upon the rate and other conditions at whichthe reaction takes place. Scanning Electron Microscope examination hasshown that precipitated calcium carbonate is distributed onto the fibersand fibers and on the spaces between them within a Minute Fibrilnetwork. Precipitated particles that adhere to fibril surfaces areespecially useful as they can modify the stiffness and hardness of thenetwork and can thus improve the abrasion properties of the network.Composition comprising in situ precipitated particle were found to beeffective in removing strong build up biofilms.

Further examples of solid particles are provided in Table 3.

TABLE 3 Product Source Wool CMW80; Dia.: 20-30 μm (>90%); Length:Goonvean Fibres Max: 200 μm (>95%) (goonveanfibres.com) Nylon(Polyamide) Fibre WN60; Dia.: 10-20 Goonvean Fibres μm ± 10% (>95%);Length: Max: 250 μm (>90%)(Average (>50%): ~125-250 μm Viscose FibreRM60; Dia.: 8-25 μm ± 10% Goonvean Fibres (>95%); Length: Max: 250 μm(>95%)(Average (>50%): ~100-225 μm Olive Stone Grit EFOG; Max: 355 μm(>99%); Goonvean Fibres Passing: 200 μm (<15%); Passing: 150 μm (<4%)Silica Syloid EXF 150 (150 μm) W. R. Grace Co., Columbia, MD SilicaSyloid EXF 350 (350 μm) W. R. Grace Co. Silica Syloid EXF 500 (500 μm W.R. Grace Co. Hydrocarb 60-FL 78% 3996200 Omya Inc., Cincinnati, OHHydrocarb PG3-FL 73% Omya Inc Omya Syncarb S160-HV 20% 4430400 Omya IncOmya Syncarb S240-HV 20% Omya Inc Silica Gel, 200-425 meshSigma-Aldrich, Inc., St. Louis, MO Silica Gel, 28-200 meshSigma-Aldrich, Inc. Calcium Carbonate Sigma-Aldrich, Inc.

Carrier Fluid Components

The gel or Minute Fibrils (or both) are suspended in a carrier fluid,such as without limitation an aqueous fluid. Typically, there will be asurfactant component configured to help loosen the attachment of acontaminant to a surface.

Surfactants or Dispersants

In embodiments of the invention, the fluid composition can comprise asurfactant or a surfactant package or mixture containing one or moresurfactants. During for example preliminary cleanup of a medical device(the bedside prep phase), surfactants can prevent and decrease strongadhesion of patient's biological material such as fecal matter, blood,mucus, protein and organisms that has recently contacted the surface ofan endoscope or device, and also can help to prevent drying of suchmaterial onto surfaces. Surfactants can also promote wetting ofhydrophobic surfaces and prevent de-wetting of surfaces by promotingformation of a thin film on the surface if drainage of composition wouldtake place. Surfactants also can help in the removal of such materials(organic soils, biofilms, organism and patient materials such as fecalmatter) from the surfaces and can lower the adhesion force ofcontaminants with the surface. A surfactant package (which can be acombination of more than one surfactant) can use a nonionic surfactant,or can use an anionic or cationic surfactant or an amphoteric surfactantor a mixture comprising various different surfactants. Examples ofsurfactants that can be used include sodium dodecyl sulfate; alkylethoxylates; amine oxides; amphoteric betaines; alkyl sulfonates; alkylphenosulfonates; fluorosurfactants; and the like. Sodium dodecyl sulfate(SDS), which is an anionic surfactant, is known to penetrate and helpdislodge biofilm. Other surfactants can be used to make the compositionsof invention without limitation as provided for example in Milton J.Rosen Monograph “Surfactants and interfacial phenomena”, third edition,Wiley Interscience (2004), and in “Surfactants—A Practical Handbook”,Edited by K. Robert Lange, Hanser Publisher, Munich (1999).

Suitable anionic surfactants include fatty acid soaps covering a rangeof alkyl chain length, for example up to about 18 carbon atoms, and maybe straight or branched chain alkyl groups. These surfactants arenormally used at a pH higher than the dissociation constant of theircorresponding carboxylic acid. Another class of anionic surfactants thathas been found to be effective with the present method is alkyl sulfatesand sulfonates, such as SDS. Another useful anionic surfactant may bebased on alkylpolyoxyethylene sulfate. Another anionic surfactant thatcan be used is an alkylbenzene sulfonate. Linear and branched chainalkylbenzene sulfates with one or more sulfonate groups have been foundto be useful. Suitable anionic surfactants also include alpha-olefinsulfonates, monoalkyl phosphates, acyl isothionates, acyl glutamates,N-acyl sarcosinates and alkenyl succinates and the like that have ananionic surface group and possess surface activity.

Suitable amphoteric surfactants include for example alkyldimethylamineoxides, alkylcarboxy betaines, alkylsulfobetaines, amide-amino acid typeamphoterics and others that may exhibit amphoteric and surface activity.Amphoteric substances have characteristics of both acid and alkaligroups.

Useful nonionic surfactants include for example polyoxyethylene alkylethers, polyethylene alkylphenyl ethers, polyethylene fatty acid esters,sorbitan fatty acid esters, polyethylene sorbitan fatty acid esters,sugar esters of fatty acids, alkyl polyglycosides, fatty aciddiethanolamides, fatty acid monoglycerides, alkylmonoglyceral ethers,fatty acid polypropyleneglycol esters and the like.

Useful cationic surfactants include for example alkyltrimethylammoniumsalts and their phosphonium analogues, dialkyldimethyl ammonium salts,alkylammonium salts, alkylbenzyldimethylammonium salts, alkylpyridiniumsalts and the like which bear cationic functional groups and possesssome surface activity.

Polymeric dispersants can also be used. Although they do not have themolecular structure of a typical surfactant, they have similar effects.These include formaldehyde condensates of naphthalene sulfonate, sodiumacrylates or copolymers of other acrylic acids, copolymers of olefinsand sodium maleate, lignin sulfonates, polyphosphates, silicates andpolysilicates, carboxymethyl cellulose, cationic cellulose, cationicstarches, polyvinyl alcohol, polyethylene glycol, polyacrylamides,polyethylene oxide/polypropylene oxide block copolymers (e.g., di- andtri-block), and the like. These compositions are also useful herein tofunction substantially as surfactants. There are also detergentsubstances which are not strictly surfactants. Examples includetrisodium phosphate, sodium carbonate and polymers. Such substances canalso be used with the present invention.

Solvents, Cosolvents

The carrier fluid or vehicle for the gel or Minute Fibrils, such as anaqueous carrier fluid, can comprise an organic solvent and optionallycan further include a co-solvent. A co-solvent is a second solvent addedin a smaller quantity than the primary solvent to enhance the dissolvingability of the primary organic solvent. The solvent and optionally theco-solvent can help to remove substances such as protein or organicsoil. Organic soil can be protein, lipids, carbohydrate, hemoglobin orsimilar substances. The solvent and the optional co-solvent can be forexample propylene glycol or a glycol ether. Solvents such as propyleneglycol and glycols ethers (from e.g., DOW Chemical Company) and otherscan be useful in the compositions of the invention because theycontribute to achieving high-level removal of lipids and some proteinsfrom endoscope channels and from external surfaces of medical orindustrial devices.

The term propylene glycol is intended to refer to any enantiomer orisomer of propylene glycol, either alone or in combination. Thisincludes a-propylene glycol (propane-1,2-diol) and β-propylene glycol(propane-1,3-diol). Propylene glycol is highly miscible with water andalso is able to dissolve various organic substances.

Glycol ethers are a group of solvents (often termed “cleaners”) based onalkyl ethers of ethylene glycol or propylene glycol. Most glycol ethersare water-soluble. They are also able to dissolve various organicsubstances. As non-limiting examples, glycol ethers include at least thefollowing substances: Ethylene glycol monomethyl ether(2-methoxyethanol, CH3OCH2CH2OH); Ethylene glycol monoethyl ether(2-ethoxyethanol, CH3CH2OCH2CH2OH); Ethylene glycol monopropyl ether(2-propoxyethanol, CH3CH2CH2OCH2CH2OH); Ethylene glycol monoisopropylether (2-isopropoxyethanol, (CH3)2CHOCH2CH2OH); Ethylene glycolmonobutyl ether (2-butoxyethanol, CH3CH2CH2CH2OCH2CH2OH); Ethyleneglycol monophenyl ether (2-phenoxyethanol, C6H5OCH2CH2OH); Ethyleneglycol monobenzyl ether (2-benzyloxyethanol, C6H5CH2OCH2CH2OH);Diethylene glycol monomethyl ether (2-(2-methoxyethoxy)ethanol, methylcarbitol, CH3OCH2CH2OCH2CH2OH); Diethylene glycol monoethyl ether(2-(2-ethoxyethoxy)ethanol, carbitol cellosolve,CH3CH2OCH2CH2OCH2CH2OH); and Diethylene glycol mono-n-butyl ether(2-(2-butoxyethoxy)ethanol, butyl carbitol,CH3CH2CH2CH2OCH2CH2OCH2CH2OH). The commercial product Carbitol™ (The DOWChemical Company) is a glycol ether, Diethylene Glycol Monoethyl Ether,which can be used as a co-solvent.

Other solvents and co-solvents beyond those named can also be used, suchas esters or ketones (such as water-soluble such compounds), andalcohols.

In embodiments, the solvent is not primarily aqueous.

pH Adjustment

In embodiments of the invention, the composition can include an additivethat adjusts the pH of the composition in a desired direction. Examplesof substances that can adjust the pH of a solution in the alkalinedirection include sodium hydroxide, sodium phosphate and sodiummetasilicate. For adjusting the pH of the solution in the acidicdirection, HCl or other organic or inorganic acids can be used, therebyproviding compositions of lower pH. A pH range between about 3 to 11.5can be useful for the formulations of invention. A basic or acidic rangecan be chosen in light of anticipated contaminants A cleaning cycle withone pH can be followed with one configured for another pH. A pH rangebetween 7 and 11 can be favorable for cleaning of endoscopes and similardevices. A composition of any desired pH can be formulated and useddepending on the surface and on the contaminants to be cleaned.

Buffers

In embodiments of the invention, the composition can include an additiveto help maintain a desired pH of the composition. Appropriate bufferingadditives can include acetate, citrate, phosphate, tris-buffer and otherknown buffers as is known in buffering systems in chemistry and biology.Other buffering systems, especially bicarbonate and phosphate, are alsosuitable in the compositions of the invention. Phosphate can be used tokeep the pH of the composition between 7 and 11, which may be favorablefor cleaning of endoscopes and similar devices. A buffer based on sodiumhydroxide and tri-sodium phosphate can also be used to make the carrierfluid.

Builders and Chelating Agents

In embodiments of the invention, the composition can include chelatingagent(s) that can sequester calcium and other multivalent cations thatcan stabilize built-up solid matter. This can help in killing bacteriaand in facilitating cleaning especially if the water used has somehardness or containing multivalent cations such as calcium. RemovingCalcium can disrupt cell walls, which in turn can make the contaminanteasier to remove. Removing calcium also can prevent the formation ofscale if tap water is used for certain processing steps later. Examplesof such a chelating substance include EDTA (ethylenediamine tetra aceticacid); tetra sodium ethylene diamine tetraacetic acid (availablecommercially as Versene™ from DOW Chemical Company); sodiummetasilicate; phosphates including polyphosphates; and similarsubstances. The compositions can include builders, similar to chelatingagents that sequester ions such as calcium or magnesium ions. Anexemplary builder is sodium tripolyphosphate (STPP).

Antimicrobial Agents and Antibiotics

In embodiments of the invention, the liquid composition can include anantimicrobial additive. It should be understood that the termantimicrobials is intended to include any one or more of variouscategories of substances, such as antimicrobials, antiseptics,disinfectants, biocides, antibiotics, virucides, prion-inactivatingagents, antifungals, antiparasitics, and the like. Antimicrobialsubstances include drugs, chemicals, or other substances that eitherkill or slow the growth of microbes. The category also includes any of alarge variety of chemical compounds and physical agents that are used todestroy microorganisms or to prevent their growth or development.

Alcohol, and alcohol in combination with other compounds, is a class ofproven surface sanitizers and disinfectants. A mixture of 70% ethanol orisopropanol diluted in water is effective against a wide spectrum ofbacteria. The synergistic effect of 29.4% ethanol with dodecanoic acidis effective against a broad spectrum of bacteria, fungi, and viruses.Sometimes an alcohol can be combined with a quaternary ammoniumantimicrobial such as is described herein.

Another category is aldehydes, such as formaldehyde, glutaraldehyde, orortho-phthalaldehyde. These compounds have a wide microbiocidal activityand are sporicidal and fungicidal.

Agents such as chlorine and oxygen that are strong oxidizers, are widelyused for antibacterial purposes. Examples of such oxidizing agentsinclude: sodium hypochlorite (commonly known as bleach), one of whoseprecursors is dichloroisocyanurate; other hypochlorites such as calciumhypochlorite (it can be noted that hypochlorites yield an aqueoussolution of hypochlorous acid that is the true disinfectant, withhypobromite solutions also being used sometimes); electrolyzed water or“Anolyte,” which is an oxidizing, acidic hypochlorite solution made byelectrolysis of sodium chloride into sodium hypochlorite andhypochlorous acid (the predominant oxychlorine species beinghypochlorous acid); chloramine, which is often used in drinking watertreatment; chloramine-T (which is antibacterial even after the chlorinehas been spent, because the parent compound is a sulfonamideantibiotic); chlorine dioxide (with sodium chlorite, sodium chlorate,and potassium chlorate being used as precursors for generating chlorinedioxide); hydrogen peroxide (which is used in hospitals to disinfectsurfaces and it is used in solution alone or in combination with otherchemicals as a high level disinfectant; is sometimes mixed withcolloidal silver); iodine, sometimes in the form of tincture of iodine,or alternatively a commercially available product known asPovidone-iodine; peracetic acid, which is a disinfectant produced byreacting hydrogen peroxide with acetic acid; performic acid, which isthe simplest and most powerful perorganic acid; other perorganic acids;potassium permanganate (KMnO4); and potassium peroxymonosulfate.

Quaternary ammonium compounds, sometimes referred to as “quats,” are alarge group of related compounds. These substances are biocides thatalso kill algae. Examples include benzalkonium chloride, benzethoniumchloride, methylbenzethonium chloride, cetalkonium chloride,cetylpyridinium chloride, cetrimonium, cetrimide, dofanium chloride,tetraethylammonium bromide, didecyldimethylammonium chloride anddomiphen bromide. Biguanide compounds, including chlorhexidine (CHX) andpolyhexamethylene biguanide (PHMB), represent another class of cationicantimicrobial compounds that are effective against a wide spectrum oforganisms. Specifically, biguanides are attractive antimicrobials foruse in the present invention because resistant strains have not appearedsince their discovery more than 50 years ago.

Phenolics are active ingredients in some household disinfectants, somemouthwashes and in disinfectant soap and handwashes. They include thefollowing substances: phenol (formerly called carbolic acid);o-Phenylphenol, which is often used instead of phenol, since it issomewhat less corrosive; Chloroxylenol; hexachlorophene; thymol (aphenolic chemical found in thyme); amylmetacresol; and2,4-dichlorobenzyl alcohol.

Still other known antimicrobial substances include: silver dihydrogencitrate (SDC), which is a chelated form of silver that maintains itsstability; biguanide polymer; polyaminopropyl biguanide; sodiumbicarbonate (NaHCO3), which has antifungal properties; lactic acid;copper-alloy surfaces. In the 1940s and early 1950s, studies showedinactivation of diverse bacteria, influenza virus, and Penicilliumchrysogenum (previously P. notatum) mold fungus using various glycols,principally propylene glycol and triethylene glycol.

Antibiotics including all classes [see e.g. Anthony RM Coates, GerryHalls, and Yanmin Hu, “Novel classes of antibiotics or more of thesame?”, Br J Pharmacol. 2011 May; 163(1): 184-194] can also be used asantimicrobial agents in the compositions of the invention.

Viscosity modifiers and Gel-forming substances

In embodiments of the invention, the composition can include a gelforming substance or a viscosity modifier. For example, a Minute Fibrilformulation can be further modified with a gel forming substance (notcomprising Minute Fibrils) or a viscosity modifier.

A viscosity modifier can be a substance that, when dissolved in water oran aqueous solution or a carrier fluid used in the invention, increasesthe viscosity. Examples of such substances include: carboxymethylcellulose, hydroxyethylcellulose; hydroxy propyl methyl cellulose;polyvinyl alcohol; polyvinyl acetate copolymer; polyvinyl pyrrolidone;and the like. Such additives can increase the viscosity of water fromits ordinary value of approximately 1 centipoise to a value in the rangeof 500 to 10000 centipoise (mPa·s) or more. Such property can also workas a suspending agent to prevent possible separation of components,provide stability, and provide a composition with a longer shelf life.Other polymers that can increase the yield shear stress and stiffness ofthe gel network such as carbopols and the like can also be used asdescribed elsewhere herein

In embodiments of the invention there can be provided gels, which can behomogeneous gels (without fibers or Minute Fibrils), which can behydrogels. Such gels provide a viscosity greater than the viscosity ofwater such as in the range between 100 to 10,000 centipoise or higher.For a description such as this, realizing that for a non-Newtonian fluidthe viscosity is a function of shear rate, the viscosity discussed canbe an average or effective viscosity at conditions of interest forcleaning applications. Such viscosity can be the value of the viscositythat, when used in the Hagen-Poiseuille Law, best correlates an observedvolumetric flowrate and an observed pressure drop. A homogeneouscomposition can be made with small molecular weight viscosity enhancingcompounds such as glycerol or sugars, or from macromolecules eithercellulosic or non-cellulosic, or from inorganic gel forming substancessuch as silica or clays including laponite, hectorite, bentonite orothers. Such gels, even if they do not contain solids or fibers (asdescribed elsewhere herein), can have usefulness for decontamination.Compositions based on homogeneous gels can be for storage of a medicaldevice or an article, as discussed in various places herein. Also, suchgels can have some usefulness for cleaning as described elsewhereherein.

A factor that can influence the choice of a gel forming agent orviscosity modifier is the ease with which that substance can be rinsedfrom the channel after residing in the channel. Some gel-formingsubstances are very soluble in water, which contributes to their abilityto be rinsed out. For example, polyethylene oxide (PEO) and polyethyleneglycol (PEG) of intermediate or high molecular weight are highlywater-soluble and are easy to rinse out. As long as such compositionscan hold a sufficient amount of various additional substances, they canbe useful according to embodiments of the invention.

Hygroscopic Additives

In embodiments of the invention, especially if a composition is intendedto remain inside a passageway of a medical device, or in contact with asurface, for an extended period of time (e.g., for storage), the fluidcomposition can be hygroscopic or can contain a humectant, so as toinhibit drying over extended periods of time. Drying can increase theadherence of contaminants. Hygroscopic or humectant additives include:propylene glycol; hexylene glycol; butylene glycol; glyceryl triacetate;neoagarobiose; sugar alcohols (sugar polyols) such as glycerol,sorbitol, xylitol, maltitol; and the like. Some substances that serve asviscosity modifiers or gel formers can also serve this purpose. Otherhygroscopic additives include: polyvinyl alcohol; polyethyleneglycol;hydroxypropylmethylcellulose; polyacrylic acid (available as Carbomer®);polyvinyl pyrrolidone. These substances are hygroscopic as well ashydrophilic. There is a tendency for hydrophilic substances to also behygroscopic to at least some extent.

Preservative

In embodiments of the invention, the composition can include apreservative, especially for some of the compositions. For example, itcan be appropriate to include a preservative in compositions thatcontain ingredients such as guar gum, xanthan gum, carrageenan, or othersubstances which could support the growth of bacteria. Such apreservative can for example be sodium benzoate, benzoic acid, methylparaben or other preservative compounds at concentrations that preventgrowth and provide a product shelf life of about one year or more.

Adjuvants

Compositions of embodiments can include a number adjuvants (color,preservative, suspending agent, flavor, and others as known in the art).Appropriate additives for these purposes can be used.

Taking into account the just-described types of additives andingredients, following are some possible formulations of carrier fluids,more specifically aqueous carrier fluids that can be used in embodimentsof the invention.

Exemplary Carrier Fluid 1

Recited in Table 4 is an exemplary carrier fluid, which may bereferenced as “CS-19.”

TABLE 4 Function or category of Component Conc., g/L substance NaOH 0.48pH adjustment agent Tetrasodium pyrophosphate 15 Suspending agent SMSsodium metasilicate 3 Increases pH, chelating agentEthylenediaminetetraacetic 23.1 Ca sequesterant, tetrasodium acid(39%)EDTA Accusol 445N 15 Dispersant polyacrylic dispersant DehypoundAdvanced 6 Surfactant nonionic low foaming Dehydol OD 5 1.5Co-surfactant that functions synergistically with the first surfactant1,2 Propanediol 2.5 Organic Solvent for facilitating removal of oilycontaminants Triethanolamine 5 Adjuvant and pH adjustment

ACUSOL 445N is a homopolymer of acrylic acid with an optimized molecularweight to be used in applications such as: liquid fabric wash, laundryadditives, industrial and institutional detergents (Rohm and HaasCompany, Philadelphia, Pa.). Dehypound Advanced is believed to beCaprylyl Glucoside and Decyl Glucoside and Deceth-5 and PPG-6-Laureth-3(BASF Corporation, Florham Park, N.J.). Dehydol is a laureth-4 polymerused as a nonionic emulsifier (BASF Corporation, Florham Park, N.J.).

Exemplary Carrier Fluid 2

Recited in Table 5 is an exemplary carrier fluid, which may bereferenced as “Modified CS-19.”

TABLE 5 Function or category of Component Conc., g/L substance NaOH (50%by weight 0.08 pH adjustment agent solution) Tetrasodium pyrophosphate2.5 Suspending agent SMS sodium metasilicate 0.5 Increases pH, chelatingagent Versene (39%) 3.85 Ca sequesterant (tetrasodium EDTA) Accusol 445N2.5 Dispersant polyacrylic dispersant Dehypound Advanced 1 Surfactantnonionic low foaming Dehydol OD 5 0.25 Co-surfactant that functionssynergistically with the first surfactant 1,2 Propanediol 20.42 OrganicSolvent for facilitating removal of oily contaminants Triethanolamine0.83 pH adjustment 1 Methyl-2 Pyrrolidone 10.0 Cosolvent/cleaner GlycolEther (DPM) 10.0 Solvent/cleaner

DPM is Dipropylene Glycol Methyl Ether CH3O[CH2CH(CH3)O]2H (One ofseveral isomers) (obtained from Dow Chemical).

Rinsing

Rinsing can be performed with water that is warm, preferably at about30° C. to about 45° C. In embodiments of the invention, rinsing can beperformed with water or aqueous composition that is sterile or free ofbacteria and organisms. Such water or aqueous composition can beproduced by filtration or it is possible to use a small concentration ofantimicrobial disinfectant or sterilant, for example such as a lowconcentration of peracetic acid. Rinsing can be performed with waterthat is deionized, produced by reverse osmosis or produced bydistillation, etc. During a rinsing process, a real-time testingprocedure can be used to determine when adequate rinsing has beenachieved, including spectroscopic methods, conductivity, special teststrip, surface tension or other appropriate methods testing thecomposition of the liquid exiting from the device. Testing can be forthe polymer components of the cleaning composition.

In past work by some of the same inventors as listed on this patentapplication (such as U.S. Pat. Nos. 6,454,871 and 6,857,436 and8,226,774), it has been demonstrated that two-phase liquid-gas flow iseffective for removing such polymeric material from narrow channels. Insuch a procedure, a typical ratio of liquid to gas, on a volumetricbasis, that can be used is about 1:1000. In general, for a common set ofconditions such as maximum allowable pressure drop across a flowpath,two phase flow is capable of much better cleaning than simple liquidflow. Thus, if needed, two-phase flow can be utilized.

For rinsing, turbulent flow can be utilized. After rinsing, alcohol andthen air can be passed through the channels to dry them. It can beassumed that the turbulent regime exists at a Reynolds number of greaterthan approximately 2000, although there is known to be a transitionregion in the vicinity of that number.

For purposes of determining the Reynolds number, the velocity used incalculating the Reynolds Number would be a bulk velocity (volumetricflowrate divided by cross-sectional area), and the viscosity used wouldbe a viscosity that, when substituted in the Hagen-Poiseuille equation,correlates the observed volumetric flowrate with the observed pressuredrop. The viscosity of the cleaning composition will likely be muchlarger than the viscosity of the rinsing composition as describedelsewhere herein. The rinsing composition may have a viscosity that issimilar to the viscosity of pure water. For an endoscope channel havingpassageways along its length, the selection of flow conditions for bothcleaning composition and rinsing composition will likely be influencedby a need to stay within an overall pressure drop across the length ofthe passageway which is typically about 2-3 atmospheres. It is possiblethat the flow of the cleaning composition may be laminar because of thetypically large viscosity of the cleaning composition. It is believedthat the use of turbulent flow during rinsing may be helpful if thegeometry of the passageways has geometric irregularities such asexpansions or branches. For example, such irregularities may be placeswhere it is especially difficult to adequately rinse out the cleaningcomposition. It is believed that with turbulence, the flow of therinsing composition may spread more thoroughly and quickly intoirregular geometries, thereby producing better rinsing. Currently theprofession does not appreciate the importance of turbulent flow andturbulent mixing during rinsing.

Optional Minimization of Lubricious Substances

In certain embodiments it can be appropriate to be judicious withsubstances that have the property of being lubricious when in their pureor nearly-pure form. Although it is common to think of oily substancesas being lubricious, additional substances can be lubricious, includingwater-soluble or water-miscible substances to be lubricious. Alubricious substance may lessen the probability of a fibril or anabrasive particle coming into contact with a surface that is desired tobe cleaned, and such lessening of contact may lessen shear or abrasiveaction acting on a contaminant. Substances for which the amount can belimited to less than lubricious amounts can include: glycerol; glycerolesters; glycerol oleate; glycerol stearate; carboxymethyl cellulose;hydroxypropylmethylcellulose; propylene glycol; esters of fatty acids;long-chain hydrophobic surfactants; sodium laureth sulfate;behentrimonium chloride/amodimethicon; simethicone; and other siliconecompounds.

Shear Thinning and Substantial Plug Flow

Shearing thinning useful in the invention is illustrated by FIG. 3,wherein the viscosity of various aqueous compositions of 1.4% w/wcellulosic Minute Fibrils (of Exilva Forte (Ef), Exilva plano (Ep) andExilva plano light (Epl), as indicated in the Figure) is shown as afunction of the rpm of the paddle used in the testing device. Thetesting device used is an Anton Parr Physica Model 501 Rheometer.

In embodiments, the cleaning compositions show shear thinning from 5 rpm(shear rate of 3.33/sec) to 30 rpm (shear rate of 20/sec) by a viscosityreduction factor of about 2-fold or more, or by about 3-fold or more, orby about 4-fold or more.

In FIG. 4, there is a sharp decrease in slope for the pressure seen at aflow rate of about 20 mL/min The test was for a 1.4% composition ofExilva forte pumped through a 12 ft. length of 3.2 mm ID PTFE tubing.The figure shows, starting from the origin and for a certain range(here, to about 20 mL/min), the pressure drop rises monotonically withflowrate. Then, above a certain flowrate, there can be reached a sort ofplateau, or at least a region in which the increase is not so rapid(here, about 22 mL/min to about 58 mL/min). Then, above a still largerflowrate, the pressure drop again increases with flowrate, or increasesmore steeply than in the plateau region. The details of such acharacteristic can vary with the composition. It is believed, althoughit is not wished to be limited to this explanation, that the firstregion corresponds to what might be called plug flow, in which thenetwork in the central part of a cross-section remains largely intact,and shear and disruption of the network occurs mostly near the wall orboundary. The plateau region of the characteristic is believed tocorrespond to a situation in which disruption of the network occurs morewidely. It is believed that the third region of the characteristiccorresponds to a situation in which the network is fully disrupted. Onecan obtain useful cleaning in the other regions, but cleaning seems tobe more efficient in the first or plug flow region.

Yield shear stress—Elasticity

The rheology of a viscoelastic material can be described by a complexmodulus. Rheometry equipment for use with this invention applies anoscillatory stimulus to the material, and measures response in terms ofboth amplitude and phase angle. This can measure a complex modulus,which can be divided into two parts. The complex modulus contains thestorage modulus G′, which describes the elastic properties, and G″, theloss modulus, which describes the viscous properties. Both quantitieshave units of Pascals or similar units. The storage modulus G′ is likean elastic modulus in a situation of elastic deformation. The lossmodulus is related to viscosity in a flow situation. The measurementfurther yields the yield shear stress. An Anton Paar Physica RM 501Rheometer operating with a 25 mm and a 50 mm parallel plate at 1 mm or2mm gap distance is used. G′ and G″ measurements were performed as afunction of strain rate in rad/s. In addition, amplitude sweeps wereperformed as a function of shear stress (Pa). All measurements are madeat room temperature.

Without being bound by theory, Applicant posits that a composition witha high storage modulus G′ will have greater cleaning efficiency.Accordingly, storage modulus G′ of at least in the tens of Pa, andperhaps in the hundreds of Pa or even higher, is desirable. It isproposed that if the storage modulus G′ or the yield shear stress of thecomposition is larger than the modulus of the contaminant (which isbelieved to be in the single digits of Pa or low tens of Pa fortraditional biofilm, and in the tens of Pa for BBF), the cleaningefficiency will be higher. It is further proposed that it is desirablethat the storage modulus G′ of the composition is larger than the lossmodulus G″.

For a material that has a yield shear stress, it can be envisioned thatin an open-topped container of the material, a load can be applied to aportion of the exposed surface, and up to a certain load, the surface ofthe material will deform simply in an elastic manner without theapplicator breaking through the surface. At a sufficiently large load,the load will penetrate through the exposed surface of the material andwill travel creating a pattern of flow around the applicator of theload. The load at which the behavior changes from elastic deformation toflow corresponds to the yield shear stress. For a material that has ayield shear stress and contains a network of entangled fibrils, it isbelieved that the measured yield shear stress is descriptive of thestrength of the network of entangled fibrils. The storage modulusdescribes yield shear stress the elastic properties or stiffness of thenetwork.

Minute Fibril compositions can produce a network structure havingsignificant yield shear stress at relatively lowconcentrations/consistency. The yield shear stress is an indication ofthe strength of the network. Yield shear stress vs. weight % of Exilva(Borregaard) in water is given in Table 6. The yield shear stressexhibited by inventive compositions is believed to arise from fiber orfibrillated entities entangled or crowded or connected to together inthe network. This network can be broken up or destroyed at higher shearrates or when the shear stress exceeds the yield shear stress formingflocs and network fragments. The actual mechanisms regarding breakdownof network are not clearly understood and we do not wish to be bound bytheory.

The ability to develop networks that have yield shear stress in therange between about 0.1 to 100 Pascal and preferably between about 5 orabout 20 Pascal to about 50 or about 60 Pascal can be useful forproducing cleaning compositions that are predisposed to be retained in achannel for a period of time, and, at the same time be thereafterreadily discharged and thoroughly cleared from the channel due to ashear-thinning character (which can be strong). Networks with higheryield shear stress from about 10 to 60 Pa can possess reasonablestrength such that during flow they can make contact with contaminantsat the tube wall and effect the removal of the contaminants from thechannels. Yield shear stress is considered a parameter that can predictthe extent of entities making contact with channel surface duringcleaning. It can be seen in Table 6 that a base concentration of MinuteFibrils can form network structures that have a yield shear stressfavored for such embodiments involving retention and flow. For certainembodiments, a yield shear stress for the composition of between about0.1 or 1.0 Pa and about 200 Pa is useful, and in other embodimentsbetween about 5.0 or about 20 Pa and about 60 or about100 Pa is useful.

TABLE 6 Concentration of Exilva Yield Shear Stress, Forte (w/w) Pa 0.1%0.03 0.5% 0.3 1.4% 41

The yield shear stress is preferably high enough such that a plug flowcan occur without destroying the network. However, the yield shearstress alone as determined by a rheometer might not fully predict theability to make a network (for purpose of creating entanglement) or evenmore specifically to flow in a favored plug regime.

In embodiments, such as above 1% concentration of minute fibrils byweight, the G′ values were higher than G″ which implies that these gelsbehave as an elastic solid. Network gels formed at higher concentrations(>1.2% minute fibrils by weight) have considerable stiffness and yieldshear stress due to considerable fiber-fiber contacts and entanglementsof fibrillated entities.

As elucidated further in the Elasticity and Stiffness Appendix toProvisional B (identified below), it is believed that the strength ofindividual fibers determines the overall stiffness of the gel if nobundling is present. If bundling or aggregation is present, the springconstant of the bundle is observed to be strongly dependent on theinter-fiber bonding. If fibers form bundles with strong inter-fiberbonds, all fibers in the bundle behave as a continuous elastic materialand the bending modulus of the bundle scales with the fourth power ofthe bundle diameter. If such a strong bonding is not present, the fibersbehave as individual elements and the scaling of the bundle bendingmodulus merely goes as proportional to the square of the bundle diameter(asymptotically). Under mechanical deformation fibers and subgroups offibers may emerge, resulting in a mixture of bonded and unbondedsub-bundles. In such a case, the bending modulus of the bundles isdependent on the bundle diameter as where the scaling of the elasticitywith bundle diameter is not directly related to the scaling withconcentration. Accordingly, the elasticity of the network can betailored by selecting the minute fibril material concentration andproperties including dimensions of fibers or fibrils, interaction orbonding due to fiber-fiber contact and entanglement. In embodiments, theelasticity of the gel network composition can be adjusted by using amixture of minute fibril materials and by the addition of stiffeningelements of different dimensions and elastic moduli (e.g.,microcrystalline cellulose or the like) or combinations thereof.Accordingly, one skilled in the art can employ embodiments of theinvention to make a range of compositions having different properties toemploy in different applications as desired. Hence, the invention is notmeant to be limited to the exemplified materials described herein.

In additions to the mechanical properties of individual fiber andfibrils, inter-fiber interactions including fiber-fiber contacts andentanglements contribute to the gel network stiffness. MacKintosh etal., Phys. Rev. Lett., 1995, 75, 4425-4428 have predicted the dependenceof stiffness on the concentration of the fibers forming a network. Thedependence of stiffness on parameters other than concentration such asthe fiber-fiber contacts, entanglements and added stiffening elementsneed to be considered to describe the gel networks of the invention. Onthe basis of SEM micrographs and scaling of elasticity withconcentration, a model based on rod network may be valid. In such amodel, the stiffness depends on many factors including the bendingspringe constant of individual fibers.

Boundary Floc Surface Collisions

Applicant has undertaken rough estimations of the number of collisionsbetween a floc of Minute Fibrils and the surface of a channel, and hascalculated that this can be 10,000 collisions between a given boundaryfloc and the surface as the boundary floc travels 1 meter. Calculationsof this type are presented in Provisional Patent Application U.S. Ser.No. 62/402394, filed Sep. 30, 2016 (“Provisional A”), and ProvisionalPatent Application U.S. Ser. No. 62/563975, filed Sep. 27, 2017(“Provisional B,” together, the “Provisionals”). Further such modelingposits that the formation of a thin gap between contaminant particle andfiber portion nearest to the wall is sufficient to remove thecontaminant because the local shear rate (shear stress) within this gapcan exceed the shear rate averaged over the wall surface in orders ofmagnitude. Based on such modeling, the local shear stress within the gapcan be for example about 30 times larger than the average bulk shearstress. This modeling is outlined in the Provisionals.*** The modelingposits that flocs on the interior of the network (colliding flocs)collide with boundary flocs, increasing the surface collisions, andhelping to overcome the depletion layer effect that protects channelwalls from effects of fluid flow.

Biofilm that is attached to a surface can be described by a shear stressthat the biofilm can withstand before becoming detached from thesurface. It is believed that the shear strength of traditional biofilm(not crosslinked) is in the range of 5 to 20 Pa, and a shear strength ofBBF is in the range of 10 to 50 Pa. It is further believed that thecompositions of the invention can achieve bulk and localized yield shearstress and forces created during flow that are greater than orapproximately equal to the shear strength of biofilm, encouragingfragmentation and detachment of the biofilm. While it is believed thatthe local shear stress can rise to values much higher, it is believedthat the bulk shear stress provides a good rule of thumb oneffectiveness of a composition for removing a given material. Throughadjustments of composition, compositions can be formulated that havehigh yield shear stress, such as in the range of from about 1 to 100 or200 Pa, or about 5 Pa to about 50 Pa.

As also modeled in the Provisional, the Treatment Number, TN, predictsthe number of tube surface treatments (the number of times that anygiven area is contacted by Boundary Flocs) during flow. If TreatmentNumber TN is<1, the cleaning is likely not sufficient. A many-fold tubetreatment by fibers can be achieved during our cleaning with the flow ofa gel that comprises Minute Fibrils. This explains why a high level ofcleaning can take place. With parameters much like described here, theTreatment Number can be in the range of 100 to 10,000 depending on thenumber of volume changes and dimensions of flocs and their contact areawith the tube wall. In an embodiment of the invention, a calculatedTreatment Number of more than 1 is desirable, and for achievinghigh-level cleaning, a Treatment Number of greater than about 25, 50 or100 is useful.

Additional Operational Parameters for Channel Cleaning

In embodiments, the composition can be caused to flow as a relativelyintact fibrillated network at low velocities or low shear rate so that aplug-like flow is realized and the network can be intact or nearlyintact near the wall of channel. As such the flocs or fibrils at theboundary of the flowing network are believed to touch and make some formof contact with the surface of the channel or passageway and removecontaminants by direct or indirect action involving desorption,detachment, sequestration or incorporation in the network and transferof entrapped contaminants along with network to the exit of the channelor passageway. Without being bound by theory, it is believed that theaction of cleaning or removal in this case can involve direct contactswith the surface or by indirect generation of high shear stresses nearthe surface of the channel causing detachment and removal ofcontaminants. In embodiments, the linear velocity of plug networks isdiagnostic of cleaning efficacy. Exemplary linear velocities foundfavorable include those about 1.0 cm/second to about 10 cm/second.Higher linear velocity of gel network in a regime where the networkremains intact or nearly intact during flow is preferred because thisprovide shorter cleaning time. Not being bound by theory, the highestpossible linear velocity of gel network that can produce contact or nearcontact with the wall is generally preferred.

The rate of cleaning can be manipulated by adjusting for example flowvelocity, pressure drop and the concentration of the polymer material inthe composition used. Treatment times can be as short as one minute oras long as about 30 minutes or longer depending on the nature ofcontaminants but in embodiments it can be between about 2 to about 10minutes or so. Cleaning parameters can be adjusted so that the flowingnetwork can remain intact or nearly intact at the surface as describedabove. Without being bound by theory, it is believed that less effectivecleaning will generally be obtained as the fibrillated network degradeswith higher flow rates. Although direct contact of polymer material withthe channel surface may be less compared to plug-like flow of asubstantially intact network, there is still significant contaminantremoval and cleaning with such flocculated flow. For example loosebacteria and organic soil can be cleaned by flocculated flow due tolower strength compared to for example BBF.

The volumetric flow velocities used to remove biofilm from channels withID between about 1.0 mm and about 4 mm are in the range of about 5 toabout 70 ml/minute during the plug-like flow cleaning mode, and can belarger than this when the flow regime is flocculated or fragmented flow.The terms “flocculated flow” and “fragmented flow” are considered to besynonymous and denote conditions when the network is broken intofragments or flocs. Volumetric flow rates can even be in the range ofabout 100 to about 400 ml/minute depending on the channel diameter andthe flow regime.

In embodiments, narrow channel internal diameters typically are in therange of about 0.6 mm to about 6.0 mm In embodiments, narrow channelscan have length in the range of about 20 to about 350 cm or more.

Compositions can be used at temperatures in the range for example ofabout 20° C. to about 80° C.

For embodiments where the channel to be cleaned has ID of about 2 toabout 4 mm (e.g., the SB channel), the following parameters (about toabout) are illustratively useful:

TABLE 7 Flow Pressure Rate Velocity Time drop (ml/min) (cm/sec) (min)(psi) 2-4 mm Channel - Cleaning 12-75 1-5 5-15 <28 2-4 mm Channel -Rinsing  850-1400  79-174 2 <28

For embodiments where the channel to be cleaned has ID of about 1 toabout 2 mm (e.g., the Air or Water (A/W) channel), the followingparameters (about to about) are illustratively useful:

TABLE 8 Flow Pressure Rate Velocity Time drop (ml/min) (cm/sec) (min)(psi) 1-2 mm Channel - Cleaning  8-24  7-21 5-15 <28 1-2 mm Channel -Rinsing 160-170 140-150 2 <28

The fibrils can have a surface charge that can be influenced ormanipulated by the choice of various ingredients in the composition. Ifall or most of the fibrils are identically charged, they will tend torepel each other and extend away from the main fibril more than wouldotherwise be the case. This will effectively make the fibrillatedmaterial rougher on a very small scale, and in embodiments is believedto improve better cleaning. Carboxy methyl cellulose (CMC), or likecharged polymers or particles, can provide such surface charge. For atleast certain such entities, such as CMC, concentrations that providedeleterious functions, such as lubricity, are avoided. It may also bethat excess concentrations can enhance a depletion layer such that thelarger entities are sometimes kept away from contact with the solidboundary due to hydrodynamic lubrication forces. Concentration can bedetermined empirically, by testing against protein or BBF contaminants.

It is discussed elsewhere herein that the composition can containparticulate material such as MicroCrystalline Cellulose or PrecipitatedCalcium Carbonate, silica, or the like. It is believed that the presenceof such additives increases the stiffness of the cleaning composition,compared to the same composition without such additives.

The yield shear stress Ty of a cleaning composition can be adjusted byany one or more of: adding stiffening solid additives (such asMicroCrystalline Cellulose or Precipitated Calcium Carbonate or silica);formulating a mixture of polymer and fibrillated material such asfibrillated cellulose; causing the fibrils to extend by repelling eachother, such as with ionic Polymer.

Carbopol, as discussed elsewhere herein, is an additive that forms a gelthat has some structure different from the structure of fibrils ofcellulose or other polymers discussed herein (as seen by freeze fractureSEM). It is found that Carbopol can be used as a stiffening component soas to increase the yield shear stress of a formulation. Other polymerscould also be used similarly. At the same time, any other ingredientdescribed herein could also be used. This is an example of a fibrillatedmaterial and polymer mixture so as to provide an increased yield shearstress, an indicator of an increased strength of the fibrillatednetwork.

Any composition described herein can contain an antimicrobial substanceor an antibiotic.

Fibers can include those produced by the Lyocell process along withfibers produced by other processes. For example, a cleaning compositionmay comprise either or both of Exilva forte and Exilva plano lite, asdiscussed elsewhere herein, and may further comprise fibers produced bythe Lyocell process. The Lyocell process involves extruding the materialthrough spinnerets to form fibers. The US Federal Trade Commissiondefines Lyocell as a fibre “composed of cellulose precipitated from anorganic solution in which no substitution of the hydroxyl groups takesplace and no chemical intermediates are formed.” It is believed that thefibers produced by the Lyocell process are more coarse than the fibersof the various grades of Exilva. Accordingly, the fibers produced by theLyocell process can serve as abrading elements that are entangled withina fibrillated network formed by other fibrillated material.

Embodiments of the invention may comprise both fibrillated cellulose andfibrillated acrylic or other non-cellulosic materials.

Mixing Parameters for Composition Preparation

Non-uniform mixing of a composition can result in some regions that havea higher-than-average concentration of Minute Fibrils (or otherpolymer). Such local regions can pose an increased risk of clogging ofsmall orifices or similar geometric features of the endoscope or medicaldevice. Improper swelling and mixing of for example the Minute Fibrilsin the liquid vehicle can result in large size agglomerates that canalso clog small orifices during flow.

Activation of a gel refers to mixing that causes entanglement of theMinute Fibrils. As discussed elsewhere herein, it may be advantageousfor there to be a considerable degree of entanglement of the MinuteFibrils with each other, which may produce a better cleaning interactionwith the walls of the channel. In order to help achieve this, inembodiments of the invention, a stirring or mixing or homogenizationstep may be performed after initial manufacture of the composition, nearin time to the use of the composition, to increase the entanglement andimprove uniformity of the distribution of Minute Fibrils.

In embodiments, components of the composition are provided as separatecomponents, to be mixed shortly before use. Mixing apparatus, which canbe automated, can be provided.

Channel Bias

In certain circumstances it may be desirable to use one pump to flowcomposition into two or more channels. In other circumstances, thechannels may have different diameters or other variations in backpressure that make it desirable to separately pump cleaning compositionthrough individual channels.

Segmented Flow

An additional observation is that to accomplish the described cleaning,decontamination or high level disinfection, or other functions describedherein, it is not essential that a fully continuous plug of thecomposition exist in the channel or tube, especially for situations thatinvolve flow through the length of a narrow channel. For example, flowthrough the channel can be an alternating series of short segments ofthe composition alternating with segments of air or water. For example,if the respective lengths of the plugs and the air lengths or waterlengths are approximately equal to each other, the pressure drop can beabout half of what it would have been for a continuous plug of thecomposition. The lengths of composition segments and alternating air orwater segments can be varied to achieve effective cleaning while at thesame time not exceeding the pressure drop limit of the device to becleaned, such as in the case of flexible endoscopes.

Negative Pressure

For many endoscope tubes there is a limit for allowable positivepressure that should be applied to the interior of a channel. A typicalvalue for such a pressure limit is about 25 psig. In an embodiment ofthe invention, assuming that the processing is carried out in anenvironment of generally atmospheric pressure, a user can apply asub-atmospheric pressure to the discharge end of the passageway whileapplying a source pressure at or near the pressure limit to the inletend of the passageway. This can achieve an overall pressure drop acrossthe passageway that is greater than the nominal pressure limit of thepassageway. For example, such a negative pressure applied to thedischarge end of the passageway could be approximately −10 psig, whichis still not so low as to cause cavitation or boiling of water. In thisway, the pressure drop from inlet to discharge of the passageway can be25 psig—(−10 psig), or a magnitude of 35 psid. At the same time, theoutward pressure experienced by the wall of the passageway is never morethan 25 psid, and some portion of the wall of the passageway experiencesa slight but acceptable inward pressure difference.

Medical Device Prep

Illustrative of other medical devices, endoscopes after use aresubjected to a prep phase, sometimes referred to as bedside prep,intended to reduce the load of contaminants prior to more formalcleaning. The compositions of the invention can be used for thispurpose. These compositions can also be added as a follow up step tomore traditional prep procedures. If stored in channels of the deviceafter prep, the compositions can decrease the chance that bacteriare-deposit on the channel walls, allowing more of the load of bacteriaor other contaminants to wash out in the initial steps of more formalcleaning. Prep compositions can include an antimicrobial or antibioticor their mixture to further suppress growth of organism or biofilms.

The gel-like or network-based composition with a yield shear stress canbe retained as a body within the channel and making intimate contactwith its internal surfaces. Alternatively the composition can besomewhat less gel-like such that there may be some drainage from thechannel but the vacated portion of the channel is still coated withelements of the composition and thus protected from regrowth of organismor biofilm, or alternatively the composition can be still less gel-likewhere there is complete drainage of the composition but the channelwalls are still coated elements of with the composition and thus remainprotected, or alternatively the composition can be sealed in the channelby caps at the ends of the channels. For the decontamination (“prep”)phase, a composition suitable for killing bacteria or othermicroorganisms and preventing their regrowth can be chosen. The “Prep”can include ingredients for keeping the surface wet, preventing dryingand preventing adhesion of contaminants to the surface or channelsduring standing or waiting periods, and thus facilitating cleaning andremoving during subsequent rinsing and cleaning steps. During the prepstep or phase, the composition can be applied to the external confinedsurface of the device to prevent growth and biofilm formation and toprevent or decrease adhesion of contaminants to the surface of thedevice. During flow to discharge the prep composition from the channel,cleaning can also take place as well.

Device Storage

Illustrative of other medical devices, endoscopes after formal cleaningand high-level disinfection are stored in a patient-ready state. In thecurrent invention, the devices can be stored filled with storagecompositions that can be identical or similar to the compositionsdescribed here for cleaning or bedside prep. Typically they are sterile.Sterile storage fluid compositions can be used to maintain the endoscopeor device in the high-level disinfected patient-ready state. Thestorage-decontaminating compositions can remain in the endoscope fortime durations ranging from minutes to hours to days or weeks and thencan be rinsed out from the endoscope or device with a sterile liquidsuch as sterile water, sterile saline, or the like. The intimate contactof endoscope surfaces with the decontaminating sterile storagecomposition can limit or prevent biofilm formation or growth duringstorage and thus can ensure that the endoscope is free or nearly free oforganisms when it is used to treat patients after the storagecomposition is flushed out of the endoscope using a sterile solution.

A discovery applicable to storage embodiments, but also to cleaningprotocols, is that treatment with flow of the polymeric compositions ofthe invention, then leaving them in place for e.g., 8 hours furtherloosens biofilm. Thus, a cleaning protocol may call for flow to stop forabout 1, 2, 4, 8 or more hours, then resume.

In embodiments of the invention, the endoscope or device can beprocessed using application of sequence of compositions starting withthe bedside prep followed formal cleaning with the minute fibrilscomposition and finally with the storage composition after completinghigh-level disinfection. Other sequences can be used for example theendoscope can be treated with bedside prep composition followed bycleaning with the minute fibril composition only followed by high-leveldisinfection or sterilization. Other sequences are envisioned wherecleaning with the minute fibril composition is applied without thebedside prep and then followed by high-level disinfection orsterilization. One skilled in the art can devise other schemes to obtainthe desired the result depending on the device under consideration.

Oral Use

In an embodiment, the Minute Fibril composition is used for removingdental biofilm and dental plaque from teeth or oral cavity. Particlesincluding for example silica, calcium carbonate, calcium phosphate ormicrocrystalline cellulose can be added as outlined herein. Thecompositions comprise an effective base material to make a new class ofdentifrice (tooth paste), which can be specifically tailored forremoving dental biofilm, plaque and preventing gingivitis. The networkcompositions of the invention are different from current toothpasteformulation/base in that they possess a network structure that hassufficient strength to make contact with tooth surface during brushingThe stiffness of the network can in embodiments be adjusted so that thestorage modulus can be more than about 2000 Pa or more than 4000 Pasince the G′ of S. mutans can be in this range as measured in theliterature [Vinogradov et al., Biofilms, 2004, 1, 49-56]. This range ofstiffness can be achieved by inclusion of stiffening additive such asmicrocrystalline cellulose in the composition as described elsewhereherein. The composition of the embodiments includes sufficient abrasionproperties to achieve effective dental biofilm removal according newmechanisms and methods. Surfactants and other ingredients such asfluorophosphare including flavors can be included in the composition.

The Minute Fibril compositions that are effective for removing dentalbiofilm need to have sufficient strength such that when pressed over thetooth surface, with the aid or brush or applicator, it can interact andmake contact with dental biofilm resulting in effective cleaning. Theinventive network can comprise Minute Fibrils and abrading particles insufficient amount so as to remove dental biofilm in a short time, forexample in two minutes. The abrading particles can include silica,calcium carbonate at a concentration so that the particles can makecontact with the tooth surface and assist in abrading and removingbiofilm. The Minute Fibrils of the invention are cleared by the US Foodand Drug Administration for use in food especially materials that arebased on cellulose such as microfibrillated or nanofibrillatedcellulose. The composition of the invention represent a new class ofdentifrice which is different from current products that mainly dependon the action of abrasive particles.

Cleaning Contaminant Targets

Additional materials that can be cleaned with the compositions of theinvention include without limitation biofilms, mineral deposits, sludgedeposits (sewage or industria), pharmaceutical and cosmetics residues,environmental residues, food residues, skin debris and residues, makeupresidues, wound debris, residues inside and outside body of host,automobile dirt and grime, bacteria disposed on a surface in healthcaresetting, and the like. Additionally, the compositions of the inventioncan be used to increase the bonding receptivity of a surface for a newcoat of paint or polymer. In embodiments, the surface is made ready forthe new layer without providing visible scratch marks or cleaningsensitive surface such as automobiles and the like. Open Surfaces

The cleaning open surfaces can be accomplished by application of manualor automated scrubbing or by other mechanical means including automatedbrushes or the like. The large surface area of the fibrillatedstructures makes them effective in removing contaminants from such opensurfaces in distinction from already described flow inside channels. Theinventive compositions can have yield shear stress from zero to severalhundred Pascals as appropriate for the intended application. Inembodiments, the compositions for open surfaces can usefully satisfy thecondition of non-de-wetting on standing. The non-de-wetting property canbe obtained by making compositions with some yield shear stress in orderto prevent draining or de-wetting from the surface by gravity and/or byadjusting the formulation of the composition so that de-wetting can beavoided such as by adding an adhesion-promoting surfactant or polymer tothe composition.

The effective cleaning of interior surfaces of endoscope channels withnano-fibers suspended in a fluid or gel is believed to be derived fromthe motion of said nano-fibers adjacent said interior surfaces. Theefficiency of the cleaning process is believed to be increased byincreasing the nano-fiber content of the cleaning formulation, and/orincreasing the flow velocity of the cleaning formulation adjacent thesurface being cleaned. Whereas, initially, increasing the flow velocityincreases the cleaning efficiency, a point is reached wherein furtherincreases in flow velocity is believed to result in a non-uniformdispersion of nano-fibers within the fluid, and a subsequent loss ofsome cleaning efficiency.

For enclosed channels, such as the lumen of a polymer tube in anendoscope, increasing the mass flow rate of the cleaning formulationthrough the lumen increases the flow velocity of the cleaningformulation adjacent the interior surface of the lumen. for opensurfaces, other method are needed to cause the cleaning formulationadjacent to said open surfaces to flow with sufficient velocity parallelto said surface.

A first device for (and method for) cleaning open surfaces is depictedin FIG. 8, wherein a cleaning formulation 10 is expelled through adelivery tube 12 and impinges upon an open surface 16, forming an everexpanding puddle surrounding delivery tube 12. Delivery tube 12 ispositioned with tube end 14 close to, but not contacting open surface16. Cleaning formulation 10 flows through delivery tube 12, and impingesupon open surface 16, proximal tube end 14, and then flows radiallyoutward, as depicted by flow lines “F.” A stagnation zone “S” isbelieved to exist at the center of the impingement area, wherein thereis little to no fluid motion in the radial direction. Cleaningeffectiveness in this zone may be low. Beyond zone “S”, there exists anannular zone “E”, wherein the radial velocity of cleaning formulation 10is believed to be sufficient to produce efficient cleaning.

The radial velocity of cleaning formulation 10, exiting from tube end14, is proportional to the mass flow rate of cleaning formulation 10through delivery tube 12, and inversely proportional to the separationdistance between tube end 14 and a given point on open surface 16. Asthe flow continues radially, the flow velocity decreases in proportionto the radius, and in proportion to the thickening of the outward flow,and cleaning becomes less efficient. To clean large areas, delivery tube12 is moved laterally over open surface 16, such that all portions ofopen surface 16 are sufficiently cleaned.

In FIG. 9, a second embodiment of the apparatus of FIG. 1 comprises disk18, appended radially to tube end 14. Delivery tube 12 is positionedwith tube end 14 close to, but not contacting open surface 16. Disc 18extends radially from tube end 14. Cleaning formulation 10 flows throughdelivery tube 12, and impinges upon open surface 16, proximal tube end14, and then flows radially outward, between disc 18 and open surface16, depicted by flow lines “F,” to form an ever expanding puddlesurrounding the perimeter of disc 18. In FIG. 4, the annular zone “E”,wherein the radial velocity of cleaning formulation 10 is sufficient toproduce efficient cleaning of open surface 16, is larger than theannular zone “E” of FIG. 2, as the presence of disc 18 preventsthickening of the of the outward flow in the area covered by disc 18,thus, a flow velocity sufficient for efficient cleaning of open surface16 is maintained for a greater radial distance from delivery tube 12.

Apparatuses and Additional Methods for Cleaning an Open Surface

FIG. 10 shows the device of FIG. 9, wherein the disk 18 is rotated asindicated by the arrow. The science of fluid mechanics teaches that if aviscous fluid exists in a space between two parallel plates, and a firstplate is held stationary, while the second plate is moved parallel tothe first plate, a movement of the fluid layer, relative to thestationary plate is created by the viscous interaction between the fluidand the moving plate. This movement is proportional to the speed of themoving plate, and is called Couette flow. As shown in FIG. 11, theeffect of this rotation is to expand the area “E” of more efficientcleaning.

As shown in FIG. 12, (where a portion of disc 18 has been cut away,exposing a portion of underlying cleaning formulation 10) the motion ofthe fluid has a radial component “V_(r)” resulting from the flow ofcleaning formulation 10 through delivery tube 12, and a tangentialcomponent “V_(t)” created by the Couette flow induced by the rotationalmotion of delivery tube 12, with appended disc 18. These two componentsadd vectorially, to produce a flow velocity “V.”

The radial component “V_(r)” is proportional to the mass flow rate ofcleaning formulation 10 through delivery tube 12, and inverselyproportional to the distance “R” from the center of delivery tube 12.The tangential component “V_(t)” is proportional to the tangentialvelocity of disc 18, which is calculated as the product of the angularrotational velocity of disc 18 and the radial distance “R” from thecenter of rotation.

Alternatively, large open surface areas can be cleaned by flowing a gelor fluid with suspended nano-fibers through channels formed between anopen surface to be cleaned and a cleaning pad having a bottom surfaceheld in contact with said open surface to be cleaned, said bottomsurface having at least one open channel, said open surface to becleaned forming closure of said at least one open channel. Referring toFIG. 13, cleaning pad 30 has a bottom surface 32, within which is formedan open channel 34. Cleaning pad 30 has a first port 38, which connectsthrough cleaning pad 30 to an open channel 34, and a second port 40.

To clean a surface such as open surface 42, cleaning pad 30 is placedwith bottom surface 32 of cleaning pad 30 in contact with open surface42, as illustrated in FIG. 10, and a cleaning formulation 44 is injectedinto first port 38 of cleaning pad 30, and recovered from second port 40of cleaning pad 30. When bottom surface 32 of cleaning pad 30 is placedin contact with open surface 42, open channel 34 in bottom surface 32 ofcleaning pad 30, in conjunction with the portion of open surface 42which spans open channel 34 in bottom surface 32 of cleaning pad 30,forms a closed conduit connecting first port 38 and second port 40.

Cleaning formulation 44, injected into first port 38, flows through thederived conduit, and is recovered from second port 40. The flow velocityof cleaning formulation 44 is chosen so as to produce maximum cleaningefficiency of that portion of open surface 42 spanning open channel 34in bottom surface 32 of cleaning pad 30. Cleaning pad 30 is slowly movedover the entirety of open surface 42, to allow adequate time of flow ofcleaning formulation 44 for every portion of open surface 42.

While not shown, one of skill will recognized that flow can be caused bya pump, which is any device suitable to cause a composition of theinvention to flow. The devices of FIGS. 8-13 cause composition to flowinto a confined space, such that a bulk shear stress can be defined.

Sterility

Those of skill will recognize when sterility of the composition isimportant. For example, in prep cleaning, sterility may be lessimportant. Of course, antimicrobial agents or preservatives can be usedto be sure that the compositions do not provide nutrients for furthermicrobial growth. Sterilization of any component that is describedanywhere herein can be performed by steam, gamma irradiation, EthyleneOxide, electron beam, or any other known method of sterilization.

Additional Carrier Fluids

A possible carrier fluid is water, or an aqueous composition containingcertain ingredients dissolved in it. However, the carrier fluid can beother materials including for example oily or oil-based liquids. Thecarrier fluid can comprise an organic solvent, possibly containingsolutes dissolved in it. The carrier fluid can be an emulsion. Suchemulsion could be an Oil-in-Water emulsion, or a Water-in-Oil emulsion,or a microemulsion. It is still further contemplated that the carrierfluid, in its condition prior to the mixing-in of the Minute Fibrils,can be a gel. The term carrier fluid is intended to encompass all ofthese possible fluids.

Other Surfaces to Be Cleaned

The outside of the tubular portion of an endoscope tube can be cleanedfor example by placing the tubular portion of an endoscope inside alarger tube, and causing a composition of an embodiment of the inventionto flow through the annular region between the larger tube and theendoscope tube.

A medical device with which embodiments of the invention can beparticularly useful is one having a channel configured to deliver orretrieve from the interior of an animal a fluid, a diagnostic device, animaging device, or a surgical device. A diagnostic device can be, forexample, endoscopes, ultrasound probes, optical devices of all kinds, orthe like. An imaging device can be for example a fiber optic camera, adevice that emits and receives electromagnetic or sound waves or thelike. A surgical device can be for example a device that delivers astent, a cutting tool, a clamping tool, a suturing tool or the like.

Devices for perfusing organs can be cleaned with the invention. CPAPdevices (Continuous Positive Airway Pressure, a type of breathingtherapy) can also be cleaned with the invention.

Another example of a device that can be usefully cleaned is anaspirating cannula, which can also be referred to as asuction/irrigation tube. Such devices can be used for a variety ofmedical, dental and other purposes. Such devices are often much morerigid than a typical endoscope. Such devices can be made of metal, oroptionally a polymeric material that is sufficiently rigid. Also, insuch devices the flowpath is often shorter, possibly even much shorter,than in a typical endoscope. Some such devices have one passageway. Insome such cases, the passageway, especially if it is intended to be usedfor suction, can contain a vent hole. The vent hole can be covered bythe finger of a user, or not covered, as desired. In use, a source ofcontinuous suction can be connected to the proximal end of the device.The vent hole can be dimensioned such that if the vent hole isuncovered, the suction mainly is in communication with the atmosphere byway of the vent hole, and very little of the suction is felt at thedistal tip of the device. If the vent hole is covered, the suctionpassageway is in communication with the distal tip of the device and canaspirate fluids from a site that is being treated. Sometimes the venthole is elongated or teardrop-shaped so that it can be partially coveredby the user's finger, as desired, to provide fine adjustment of theamount of suction delivered. Some such devices have two passageways, inwhich case one passageway can be used for delivering a fluid such as aliquid to the treatment site, and the other passageway can be used forsuction or aspiration.

Such a device would have a path length L of the passageway, and wouldhave an inside diameter D of the passageway. For such a device, the L/Dratio might be smaller than it is for a typical endoscope channel. Also,if such a device is made of metal or is more rigid than a typicalendoscope, such a device can have passageway walls that are stronger andable to withstand a greater internal pressure. Taken together, for sucha device, these facts can allow for the flowing of fluids that are moreviscous than are permissible for typical endoscope channels, or canallow for flowing so as to create a larger shear stress at the walls.

In still other embodiments of the invention, in addition to cleaningchannels of endoscopes, inventive compositions could be used for any ofthe following purposes: as a skin scrub, such as a surgical scrub toclean the surgical field before surgery; as a substance for cleaningsebaceous (oily) skin such as for acne; as a toothpaste (dentifrice) forremoving biofilm, plaque, etc.; for cleaning the surface of aprosthesis, even a prosthesis that has already been implanted; As adebridement agent for wounds, including infected wounds; for cleaningmembranes, such as for cleaning biofouling on membranes; and forremoving mold (e.g., from building surfaces).

An example of a possible industrial (non-medical) application iscleaning the interiors of tubes of a heat exchanger. Such tubes aretypically larger in inside diameter than the already-described endoscopechannels, whose inside diameters are typically measured in millimeters.Heat exchanger tubes would typically have inside diameters that aremeasured in centimeters, and commonly they would be made of a metal.They could be cleaned by the described compositions and methods. Thedescribed compositions and methods can be used to clean any surface orpipe, such as cleaning radioactive deposits from pipes. They can be usedin the form of a ‘pig’, i.e., as a discrete plug rather than acontinuous flow of fluid, suitable to clean larger, as well as smaller,channels.

It would also be possible to use any of the described compositions ormethods to clean wafers of semiconductor material, such as silicon,during the manufacturing of semiconductor wafers or circuits orproducts.

In applications in the cosmetics industry, when microfibrillatedcellulose is used, it is typically used as a thickener (viscosityenhancer) in a formulation. The concentration of fibers is low comparedto the concentration of surfactant, and the concentration of such fibersis typically in a range such that not much entanglement is created.Thus, if there is any cleaning effect from the fibrils it is small. Thecosmetics industry prefers bacteria-originated fibrils, which are veryfine, rather than fibrils that originate from wood pulp. For skin ormucosal uses, preferably the Minute Fibril concentration is from about0.1% w/w to about 3% w/w.

Such cosmetic use can include use as a body wash, hand wash or shampoo,for use with any animal. In embodiments for cosmetic use, antimicrobialfunction is provided by appropriate essential oil(s).

The compositions of the invention can be used to clean or micro-sharpenblades.

Additionally, compositions of the invention can be used to clean theviewing screens of electronic devices, a surface of a precisioncylinder, a cylinder-engaging surface of a piston, a food preparationsurface, a surface of a gem, a glass surface.

Exemplary Minute Fibril Compositions

An exemplary base cleaning composition can comprise the materialsdefined as in Table 9:

TABLE 9 Water or solvent from about 95% to about 99% by weight about 1to about 5% Minute Fibrils or Minute Fibrils + gel-forming polymeroptional pH adjusting agent to provide a pH from about 2.0 to about 13.0The mixture forming a fibrillated network

The composition is sufficient to remove weakly adhering contaminants (itremoves such contaminants, better than the vehicle alone), such asdeposited organic soils and loose organisms mixed with the organic soiland young fragile biofilms. It may be less effective to remove mature orbuilt-up crosslinked biofilms.

With one tested Minute Fibril composition at less than 0.5% in water, nofibrillated network formed, and the composition displayed minimal yieldshear stress. When the concentration increased from about 0.5% to >2% byweight, a fibrillated network formed, which was evidenced by thecomposition having a yield shear stress of about 1.5 Pa at a fibrillatedmaterial concentration of 1% by weight, and a yield shear stress ofabout 40 Pa at a fibrillated material concentration of 1.4% by weight,as measured by storage modulus with the aid of a rheometer. Cleaningwith a fibrillated network is preferred and cleaning with a networkhaving yield shear stress of about 5 Pa to about 100 Pa (or about 5 Pato about 60 Pa, or about 5 Pa to about 41 Pa) is also believed to beuseful. Having an appropriate pH of the composition is helpful forremoving contaminants Higher pH is believed to be more favorable forremoving protein and organisms, and low pH is believed to be morefavorable for removing inorganic deposits such as inorganic scale.

An exemplary base cleaning composition can be defined as comprising thecomponents in Table 10:

TABLE 10 Water or solvent from about 95% to about 99% by weight 1 to 5%Minute Fibrils or Minute Fibrils + gel-forming polymer Optional pHadjusting agent to provide pH from about 2.0 to about 13.0 Surfactant orsurfactant mixture from about 0.01% to about 0.5% - surfactant can benonionic, anionic, cationic, amphoteric or mixture thereof) Optionallythe mixture forming a fibrillated network

An exemplary base cleaning composition can be defined as comprising thecomponents in Table 11:

TABLE 11 Water or solvent from about 95% to about 99% by weight 1 to 5%Minute Fibrils or Minute Fibrils + gel-forming polymer Optional pHadjusting agent to provide pH from about 2.0 to about 13.0 Surfactant orsurfactant mixture from about 0.01% to about 0.5% - surfactant can benonionic, anionic, cationic, amphoteric or mixture thereof) Optionallythe mixture forming a fibrillated network Stiffening or AbrasiveComponents (e.g., about 0.1% to about 5% by weight of the composition,or about 0.1% to about 3% by weight

An exemplary base cleaning composition can comprise materials defined asin Table 12:

TABLE 12 Water and organic solvent from about 95% to about 99% byweight, water comprising a major portion of the solvent component 1 to5% Minute Fibrils or Minute Fibrils + gel-forming polymer Optional pHadjusting agent to provide pH from about 2.0 to about 13.0 Surfactant orsurfactant mixture from about 0.01% to about 0.5% - surfactant can benonionic, anionic, cationic, amphoteric or mixture thereof) The mixtureforming a fibrillated network

All such compositions can comprise additional components describedherein, including antimicrobials, antibiotics, surfactants, and thelike.

Exemplary Effective Cleaning Conditions

Below in Tables 13, 14 and 15 are conditions that proved successful inremoving BBF from narrow channels. The carrier fluid was substantiallysimilar to CS-19, with the pH from about 10 to about 11.

TABLE 13 Feed Composition Int. Dia Length Main Component Additive # mmcm Desc. wt % Desc. wt % 1 1 10.16 3:1 Epl/Ef 1 None 0.0 2 1:37 10.163:1 Epl/Ef 1.2 NT200 2.0 3 1.6 10.16 3:1 Epl/Ef 1.2 NT200 1.0 4 3.291.44 3:1 Epl/Ef 1.7 None 0.0 5 3.7 10.16 3:1 Epl/Ef 1.9 NT200 2.0

TABLE 14 Feed Composition Rinse Data Weight Clean Target Δ Actual RinseRinse Reynolds to clean time Press. Flow Rate time rate No. # g minpsi/ft g/min min mL/min Re 1 19 8 1.9 2.4 1 60 1,273 2 16 8 2.7 2.0 5100 1,549 3 85 8 1.9 10.6 1 140 1,857 4 110 4 1.9 27.5 3 333 2,211 5 1408 1.8 17.5 3 333 1,912

TABLE 15 Feed Composition Data Linear Apparent Apparent Shear VelocityViscosity Reynolds stress at Shear Rate # cm/sec mPa-sec No. Re wall, Pa1/sec 1 5.0 2,774 0.02 10.7 403 2 2.3 4,682 0.01 20.8 132 3 8.8 620 0.2317.1 441 4 5.7 240 0.76 34.2 143 5 2.7 357 0.28 37.4 59

Protocol for Oil Burden Testing

For Oil burden testing, a 6 foot section of Teflon® tubing with 3.2 mmID is used. The entire tubing is filled with JIF creamy peanut butter.According to its label, this peanut butter is made from roasted peanutsand sugar, and contains 2% or less of: molasses, fully hydrogenatedvegetable oils (rapeseed and soybean), mono and diglycerides, salt.Also, according to its label, a 32 g serving contains: 190 calories, 16g fat (sat. fat 2.5 g, trans fat 0 g, chol. 0 mg), carbohydrate 8 g(dietary fiber 2 g, sugars 3 g), protein 7 g. Cleaning efficiency isviewed visually. A positive result is considered to be tubing that isvisually indistinguishable from the negative control (tubing without anypeanut butter). In embodiments, compositions of the invention remove oilburden by this test.

BBF Cleaning in a Channel

To test removal of BBF as manufactured as described herein, the middleof the channel (tubing) is cut open lengthwise and is examined by aScanning Electron Microscope and culturing. Where the positive controlshows a clear biofilm, a positive biofilm removal is shown by the twotest samples being free of the biofilm (substantially equal to thenegative control). In embodiments, the compositions of the invention aresuccessful in removing BBF.

BBF Cleaning from an Outer Surface

On open surfaces cleaning is examined by a Scanning Electron Microscope.Where the positive control shows a clear biofilm, a positive biofilmremoval is shown by the two test samples being free of the biofilm(substantially equal to the negative control). In embodiments, thecompositions of the invention are successful in removing BBF.

Bioburden Testing

For bioburden testing, a 6 foot section of Teflon® tubing with 3.2 mmInside Diameter is used. The entire tubing is filled with the AustrianSoil (iso.org; ISO/TS 15883-5:2005(E)) containing ˜10̂8 CFU/mL of each ofEnterococcous faecalis, Pseudomonas aeruginosa, and Candida albicans.The soil is left in the tubing for 2 hours.

The harvesting method for the channel is performed according to theflush-brush-flush method [Alfa et al., 2016, BMC Res Notes 9: 258; Alfaet al., 2016, J Hosp Infect 93: 83-88]. The collected sample is 40 mLsterile reverse osmosis (sRO) water and includes the tip of a cleaningbrush.

Collected samples are processed by the following sequence: 1 minutevortex, 3 times of 5 second sonication, and 1 minute vortex. Proteinquantitation is performed using the QuantiPro™ BCA Assay Kit. Bovineserum albumin is used as the protein standard (Sigma-Aldrich, St. Louis,Mo.). Hemoglobin is measured using the 3,3′,5,5′-tetramethylbenzadineliquid substrate system for enzyme-linked immunosorbent assay(Sigma-Aldrich, St. Louis, Mo.) with 80 mg/dL cyanmethemoglobin standard(Stanbio Laboratory, Boerne, Tex.). Carbohydrates are measured by thephenol-sulfuric acid with a glucose standard method. Bioburdenquantitation is performed using serial dilutions of 1:10 followed by thespread plate method using 0.1 mL of each dilution onto BBL CHROMagar™Orientation Media (Becton Dickinson, Franklin Lakes, N.J.).

A positive result is defined by: a reduction of about 99.5% or greaterin protein, a reduction of about 99.5% or greater in carbohydrate, and aReduction Factor RF for the reduction in each of the three bacteria ofabout 6.0 or higher, meaning 6 orders of magnitude. In preferredembodiments, compositions of the invention are effective in yielding apositive result regarding bioburden removal.

Specific embodiments according to the methods of the present inventionwill now be described in the following examples. The examples areillustrative only, and are not intended to limit the remainder of thedisclosure in any way.

All ranges recited herein include ranges therebetween, and can beinclusive or exclusive of the endpoints. Optional included ranges arefrom integer values therebetween (or inclusive of one originalendpoint), at the order of magnitude recited or the next smaller orderof magnitude. For example, if the lower range value is 0.2, optionalincluded endpoints can be 0.3, 0.4, . . . 1.1, 1.2, and the like, aswell as 1, 2, 3 and the like; if the higher range is 8, optionalincluded endpoints can be 7, 6, and the like, as well as 7.9, 7.8, andthe like. One-sided boundaries, such as 3 or more, similarly includeconsistent boundaries (or ranges) starting at integer values at therecited order of magnitude or one lower. For example, 3 or more includes4 or more, or 3.1 or more. If there are two ranges mentioned, such asabout 1 to 10 and about 2 to 5, those of skill will recognize that theimplied ranges of 1 to 5 and 2 to 10 are within the invention.

Where a sentence states that its subject is found in embodiments, or incertain embodiments, or in the like, it is applicable to any embodimentin which the subject matter can be logically applied.

EXAMPLE 1

This example describes a protocol for preparing biofilm for use in thedescribed experiments. This protocol produces what can be calledtraditional biofilm (“TBF”).

Preliminary Steps

1. Subculture Enterococcus faecalis ATCC 29212 and Pseudomonasaeruginosa ATCC 15442 on blood agar (BA) plates. The organisms should be24 hours old on the day of experiment.

2. Sterilize the 6-foot lengths of 3.2 mm ID PTFE tubing required fortesting, in the Steris System IE (include BI and CI). Dry thoroughly. Besure the required lengths are sterilized no more than 7 days prior totesting.

3. Prepare ATS-2015 with 20% defibrinated sheep blood (this soil can bestored up to 2 weeks in the refrigerator). The organisms will besuspended in Artificial Testing Soil (ATS) as published by Alfa et al.(Ref “Alfa et al., 2010. EVOTECH® endoscope cleaner and reprocessor(ECR) simulated-use and clinical-use evaluation of cleaning efficacy,BMC Infectious Diseases. BMC Infectious Diseases 2010, 10:20www.biomedcentral.com/1471-2334/10/200)”). The ATS soil was developed tomimic organic residues left in flexible endoscopes after agastro-intestinal endoscopic procedure, including protein, carbohydrateand hemoglobin.

Experimental

1. On Sunday night, make appropriate soil/bug suspension (EF and PA eachat ˜108 cfu/mL in ATS-2015 containing 20% sheep blood) and perform aninoculum count. Feed this suspension through the appropriate length ofPTFE tubing (pre-sterilized in the Steris System 1E) while attached to apump. Circulate the soil at pump setting 5.8 overnight (˜1.2 ml/min)—butin any case adjust the flow rate so as to maintain continuousuninterrupted circulation.

2. On Monday morning, make appropriate soil/bug suspension (EF and PAeach at ˜105 cfu/mL in 1:10 diluted ATS-2015 containing 20% sheep blood)and perform an inoculum count. Turn pump off and expel the soil from thePTFE length while still attached to the peristaltic pump tubing andreturn soil to the original container. While still attached to the pumptubing, push through (slowly) 20 mL of sRO water+30 mL of air using a 60cc luer lock syringe. Detach PTFE from the pump (clean the pump tubing)and bring the PTFE under the biological safety cabinet (“BSC”) inside acontainer. Push 30 mL of sRO water+30 mL of air through the PTFE into adiscard container. Repeat×2. Push some air through to dry the tubing.Re-soil (EF and PA each at ˜105 cfu/mL in 1:10 diluted ATS-2015containing 20% sheep blood) and attach to the pump (using new pumptubing) and circulate at pump setting 5.8 until the following morning.

3. On Tuesday through Thursday, repeat rinsing/soiling of tubing exactlyas per Monday. Soil overnight using the 105 cfu/mL soil/bug suspensionuntil Friday morning.

4. On Friday (Day 5), rinse with sRO water exactly as per previous days.Dry and perform destructive and other testing as required.

EXAMPLE 2

To make BBF, the bacteria, ATS and tubing material described above areused in the following protocol:

GROWTH STEP Rinse Glutaraldehyde Rinse ATS-Bacteria Sterile TapGlutaraldehyde Sterile Tap Inoculation: Water Rinse Exposure Water RinseDay of week (time of (20 mL (1:50 dilution; (30 mL Day of circulationwater + 30 0.05%, water + 30 END OF DAY DAY Week: using pump) mL air) 2minutes) mL air × 3) instruction: 1 Mon Growth Step: ATS-bacteriacirculates (pump setting 5.8, ~1.2 ml/min) 2 Tues Growth Step:ATS-bacteria circulates (pump setting 5.8, ~1.2 ml/min) 3 Wed GrowthStep ✓ ✓ ✓ Fill Tubing with ends at 48 h sterile water (O/N at RT) 4Thurs ✓ ✓ ✓ ✓ Fill Tubing with (4 hours) sterile water (O/N at RT) 5 Fri✓ ✓ ✓ ✓ Begin Growth (4 hours) Step 6 Sat Growth Step: ATS-bacteriacirculates (pump setting 5.8, ~1.2 ml/min) 7 Sun Growth Step:ATS-bacteria circulates (pump setting 5.8, ~1.2 ml/min) 8 Mon GrowthStep ✓ ✓ ✓ Flush some air ends (FULL STRENGTH thru channel 2.6% GLUT forto remove 20 MIN) excess fluid.

EXAMPLE 3

Rinsing Minute Fibrils

A rinsing experiment was performed in the air and water channels of anOlympus Colonoscope (Model No. CF-100L). A gel containing Exilva Forteat a concentration of 2% (by weight) in CS-19 was recirculated in theair and water channels of this endoscope for 10 hours using a meteringpump (Model No. PM60, Fluid Metering, Inc., Syosset, N.Y.). The gel wasinjected through the air-water port and air channel at the umbilical endof this endoscope, and it flowed all the way to the distal end of theendoscope. The flow rate of this gel inside the colonoscope was 8.5mL/min and the average pressure measured at the inlet of the colonoscopewas about 24 psi. The colonoscope was then rinsed with water prepared byReverse Osmosis (RO) at a flow rate of 200 ml/min for 10 minutes usingthe same metering pump. The rinsing water was also injected through theair-water port and through the air pipe at the umbilical endsimultaneously. The average pressure at the inlet of the colonoscopeduring rinsing was about 14 psi. After the completion of both thecleaning and the rinsing, a sampling procedure was performed on thiscolonoscope using a two-phase flow recovery method using 0.075% Tween-20solution and HEPA-filtered air at 28 psi set pressure. The flow rate ofTween-20 solution during two-phase flow was 16 ml/min and the airpressure dropped to about 20 psi during two-phase flow. A total volumeof about 200 ml of Tween-20 solution was used during this experimentusing two-phase flow to check the quality of rinsing. The outflow wascollected as four separate samples, which are described as follows.

Sample 1: This sample (about 40-50 ml) was collected in a transparentcup after 3 minutes of two-phase flow. We observed some long fibers andcoagulation of fibers in this sample. Also, one drop (˜0.2 gm) of thissample was put on a microscope slide and one long fiber was observedunder the microscope. Sample 2: This sample (about 40-50 ml) wascollected in a transparent cup from the 3 minute time point to the 6minute time point of two-phase flow. We observed some long fibers butfewer than with Sample 1. Sample 3: This sample (about 40-50 ml) wascollected in a transparent cup from the 6 minute time point to the 9minute time point of two-phase flow. We observed approximately the samenumber of fibers as with Sample 2. Sample 4: This sample (about 40-50ml) was collected in a transparent cup from the 9 minute time point tothe 12 minute time point of two-phase flow. We observed some fibers inthis sample but fewer than with Samples 2 and 3. Accordingly, the MinuteFibrils can be removed under practical conditions.

In a related experiment, Applicant noted that Minute Fibrils can betrapped in the air-water cylinder (spool valve region) in the handlearea, such that this area and like complex structures should becarefully rinsed.

EXAMPLE 4 Minute Fibril Flow Through 1.6 mm Channel

Exilva Forte—1%

A gel containing 1% Exilva Forte (Borregaard) gel in CS-19 wasrecirculated in the air and water channels of an Olympus Colonoscope(Model No. CF-100L) for a total of 22 hours using a metering pump (ModelNo. PM60, Fluid Metering, Inc., Syosset, N.Y.) as follows: The gel wasinjected through the air-water port at the umbilical end of thiscolonoscope and recirculated for a total of 10 hours. Then the gel wasinjected through the air-water port and air pipe at the umbilical end ofthis colonoscope and was recirculated for 6 hours. Then, the gel wasinjected through the air pipe at the umbilical end of this colonoscope(with the air-water port at the umbilical end being closed) and wasrecirculated for 6 hours.

The flow rate of gel inside the colonoscope was 8.5 ml/min and theaverage pressure measured at the inlet of the colonoscope was about 24psi. After each step, the colonoscope was rinsed with Reverse Osmosiswater at a flow rate of 200-250 ml/min for 10-15 minutes. The rinsingwater was also injected through the same port(s) as the gel and theaverage pressure at the inlet of the colonoscope during rinsing wasabout 14 psi.

No clogging was observed. This example shows that gel containing ExilvaForte at a 1% concentration can pass through the small (air and water)channels of an endoscope without clogging.

Exilva Forte—2%

A gel containing Exilva Forte at a concentration of 2% (by weight) inCS-19 was recirculated in the air and water channels of an OlympusColonoscope (Model No. CF-100L) for a total of 10 hours using a meteringpump (Model No. PM60, Fluid Metering, Inc., Syosset, N.Y.) as follows:The gel was injected through the air-water port and air pipe at theumbilical end of this colonoscope and recirculated for a total of 10hours.

The gel flow rate inside the colonoscope was 8.5 ml/min and the averagepressure measured at the inlet of the colonoscope was about 24 psi.After each step, the colonoscope was rinsed with Reverse Osmosis waterat a flow rate of 200 ml/min for 15 minutes. The rinsing water was alsoinjected through the air-water port and the air pipe at the umbilicalend of the endoscope, and the average pressure at the inlet of thecolonoscope during rinsing was about 14 psi.

No clogging was observed. This example shows that gel containing ExilvaForte at a somewhat higher concentration than in the previous example,i.e., a 2% concentration, can also pass through the small (air andwater) channels of an endoscope without clogging.

It can be noted that concentrations such as are reported here arecalculated as the dry weight of the Exilva product, compared to thetotal weight of the composition. It can be noted that the Exilva productis usually shipped wet, but for purposes of characterizing concentrationof Minute Fibrils in a composition, reference is made to weight of thefibrils when they are dry.

EXAMPLE 5 Cleaning Bioburden

In soiling experiments described herein, unless indicated otherwise,soiling was made with Austrian Soil. Following are the volumes of soilused to contaminate the channels: 10 mL for 3.2 mm ID tube and 3 mL for1.6 mm ID tube. The soil was left to stand in tube for 2 hrs, followedby cleaning and rinsing followed by harvesting of remainingcontaminants. Harvesting was done using Sterile Reverse Osmosis waterand other protocols as described elsewhere.

ATS soil as developed by Alfa (U.S. Pat. No. 6,447,990) was used as asurrogate to indicate medical device cleaning by measuring remainingprotein, carbohydrate and hemoglobin in the tube or channel aftercleaning as per the protocol described elsewhere herein. Other organicsoils simulants were also used to demonstrate embodiment of theinvention. The “Austrian Soil” was made according to ISO standard ISO/TS15883-5: 2005.

The Minute Fibril composition used in this example was 0.4%Nanofibrillated cellulose made by EFT company at a concentration of0.4%. The concentration is by weight, and refers to dry weight of thefibers in conjunction with weight of the carrier fluid. The gel was madein the CS-19 carrier fluid. The composition was made by homogenizing thefibrillated material in the CS-19 carrier fluid for 5 minutes or until ahomogeneous gel network was formed. The cleaning network composition wasstable during storing without separation. All cleaning experiments wereperformed at room temperature unless otherwise indicated. Rinsing wasdone with distilled water. The details of experiments are given in thefollowing tables.

TABLE Test Conditions for 3.2 mm inside diameter of channel: DurationFlow rate Pressure drop Temperature (min) (ml/min) (psi) (° C.) Cleaning3 280 0 RT Rinsing 3 560 0 RT

TABLE Test Conditions for 1.6 mm inside diameter of channel: DurationFlow rate Pressure drop Temperature (min) (ml/min) (psi) (° C.) Cleaning3 140 <10 RT Rinsing 3 280 <15 RT

TABLE Organic Soil Results: Channel ID = 3.2 mm, Channel ID = 1.6 mm,Length = 183 cm Length = 183 cm Conc. Conc. Conc. Conc. (μg/ml) (μg/cm²)(μg/ml) (μg/cm²) Protein (Benchmark is <6.4 μg/cm²) PC 4348 1123 3261815 NC 0.761 0.166 0.652 0.142 Cleaning Test 1 1.087 0.236 0.109 0.024Cleaning Test 2 0.652 0.149 0.217 0.047 Carbohydrate (Benchmark is <1.8μg/cm²) PC 17500 4521 17917 4483 NC 5.833 1.269 6.667 1.451 CleaningTest 1 1.25 0.272 3.333 0.761 Cleaning Test 2 0 0 7.5 1.632

PC is positive control, soiled no cleaning; NC is negative control, isbrand new tube without soil; Cleaning Test 1 and Cleaning Test 2 areduplicates of each other.

The values of 6.4 micrograms protein and 1.8 micrograms carbohydrate arebenchmarks of what is considered acceptable cleaning according toindustry as originally published by Alfa et al. For a device to beconsidered clean, the measured value for carbohydrate after cleaningmust be less than the benchmark value of 1.8 microgram/cm̂2. Cleaningwith the inventive technology achieved cleaning levels that certainlyway below this benchmark value.

The results of this example show that the measured residual proteinlevels after cleaning soiled tubes are almost the same as the negativecontrol. This indicated that almost all organic soil is removed from thechannels. In fact, results are achieved that are even cleaner than thenegative control, which means that this technology removed contaminantsthat were present from manufacturing.

The experiment was repeated with soiling was done with Austrian Soil andthe tubing was allowed to sit in a wet condition for 30 min followed byflowing air through the tubing for 1 hr 30 min to dry out the soil,followed by cleaning. Even the soil was allowed to dry in the channel,the results were substantially the same.

EXAMPLE 6 Cleaning Bioburden

This example shows the removal of ATS soil (Artificial Test Soil-T)(U.S. Pat. No. 6,447,990). This is a repeat of Example 4 with the onlydifference being that the organic soil was a different soil from thesoil that was used in Example 4. Cleaning and rinsing conditions wereidentical to those used in Example 4.

Channel ID = 3.2 mm, Channel ID = 1.6 mm, Length = 183 cm Length = 183cm Conc. Conc. Conc. Conc. (μg/ml) (μg/cm²) (μg/ml) (μg/cm²) Protein(Benchmark is <6.4 μg/cm²) PC (10⁻²) 31.141 (3114.1) 7.283 (728.3)26.913 (2691.3) 6.441 (644.1) NC 0 0 0 0 Cleaning Test 1 0 0    0.201   0.044 Cleaning Test 2 0 0 0 0 Carbohydrate (Benchmark is <1.8 μg/cm²)PC (10⁻²) 0 0  8.8 (880) 2.106 (210.6) NC 0 0 0 0 Cleaning Test 1 0 0 00 Cleaning Test 2 0 0 0 0 Hemoglobin (Benchmark is <2.2 μg/cm²) PC(10⁻²) 3.089 (308.9) 0.722 (72.2)  1.951 (195.1) 0.467 (46.7)  NC 0 0 00 Cleaning Test 1 0 0 0 0 Cleaning Test 2 0 0 0 0

Similar experiments were conducted where Enterococcus faecalis (EF),Pseudomonas aeruginosa (PA) and Candida albicans (CA) were introducedinto the soil. In those experiments, zero colony forming units wererecovered after cleaning, even for narrow 1.6 mm channels. These resultsdemonstrate that remarkable cleaning levels can be achieved even withouttraditional mechanical brushing.

EXAMPLE 7 Cleaning Bacteria—Laden Bioburden with Minute Fibrils Only

Substantially the bioburden testing with added Enterococcus faecalis(EF), Pseudomonas aeruginosa (PA) and Candida albicans (CA) wasrepeated. However the cleaning composition was: 0.4% NFC (EFTec™Nanofibrillated Lyocell Fiber Type L040-6SEFT (cellulose fibers)) in ROwater. This uses Minute Fibril structure in pure water without any otheradditives, including without surfactant. The results met cleaningspecifications for bioburden. For bacteria, the worst result was forPseudomonas aeruginosa in a 3.2 mm channel, with the result being3.00×10 (vs. positive control of 1.78×10̂8). This example shows that themechanical action of the Minute Fibrils alone is sufficient to cleanthis bioburden and organic soil. In other experiments, the inclusion ofother ingredients in the network composition further improves cleaningand decreases the cleaning times as well.

EXAMPLE 8 Cleaning Biofilm

TBF was grown in a flow reactor using multispecies organisms(Enterococcus faecalis (“EF,” ATCC 29212), Pseudomonas aeruginosa (“PA,”ATCC 27853), Candida albicans (“CA,” ATCC 14053)), as describedelsewhere herein. Six-foot sections of 3.2 mm and 1.6 mm diameterTeflon® tubes bearing the biofilm were tested for cleaning efficiencywith Minute Fibril (cellulose) gels made at 2% by weight in water orsurfactant solution at flow rates between 20-70 mL/minute. The tubeswere sampled before and after cleaning and investigated by SEM andculture methods. Positive and negative controls were used and theresults were compared with conventional manual cleaning as describedbelow in “Method.” SEM micrographs of sliced open tubing before (FIG.5A) and after cleaning (FIG. 5B) showed unparalleled/complete biofilmremoval from the surface despite the high adhesion strength known formultispecies biofilms. These positive results are supported by cultureresults of the same tube sections as summarized in the Tables below.

Biofilm removal from the 1.6 mm A/W channel was complete in repeatedexperiments, while manual cleaning could not remove the biofilm at all(FIG. 5C). Also, there was excellent removal of biofilm (more than 6 logreduction) from the 3.2 mm S/B channel, as supported by SEM and cultureresults. Overall, these very positive results demonstrate that theMinute Fibril cleaning technology has the potential of removing biofilm(matrix and organisms) from endoscopes compared to current methods. Theeffective removal of biofilm will prevent infections such as CRE.Importantly, the technology is capable of effectively cleaning biofilmfrom the narrow A/W channels that cannot be brushed with currentmethods.

TABLE 3.2 mm Channel (Sq. Area 183.851 cm{circumflex over ( )}2) RF (logcfu/cm2 cfu/6-ft Log₁₀cfu/6-ft reduction) Positive EF 1.24 ×10{circumflex over ( )}6 2.28 × 10{circumflex over ( )}8 8.357 ControlPA 2.64 × 10{circumflex over ( )}7 4.85 × 10{circumflex over ( )}9 9.686Negative EF 0 0 Control PA 0 0 Test 1 EF 0 0 8.357 PA 0 0 9.686 Test 2EF 0.28 × 10  5.20 × 10{circumflex over ( )}2 2.716 5.641 PA 2.97 × 10 5.46 × 10{circumflex over ( )}3 3.737 5.949 Manual EF 0 0 8.357 Clean PA7.85 × 10{circumflex over ( )}2 1.44 × 10{circumflex over ( )}5 5.1604.526

TABLE 1.6 mm Channel (Sq. Area 91.925 cm{circumflex over ( )}2) RF (logcfu/cm2 cfu/6-ft Log₁₀cfu/6-ft reduction) Positive EF 4.40 ×10{circumflex over ( )}6 4.05 × 10{circumflex over ( )}8 8.607 ControlPA 6.55 × 10{circumflex over ( )}5 6.02 × 10{circumflex over ( )}7 7.780Negative EF 0 0 Control PA 0 0 Test 1 EF 0 0 8.607 PA 0 0 7.780 Test 2EF 0 0 8.607 PA 0 0 7.780 Manual EF 5.54 × 10{circumflex over ( )}4 5.09× 10{circumflex over ( )}6 6.707 1.900 Clean PA 4.24 × 10{circumflexover ( )}4 3.90 × 10{circumflex over ( )}6 6.591 1.189

EXAMPLE 9 Cleaning Bioburden from an Endoscope

Soiling of endoscope was made with the ATS-T with the Enterococcusfaecalis (EF) (ATCC 29212) bacteria. EF was used because or it highdegree of adhesion to channel surface. The endoscope used was OlympusColonoscope CF-Q160L. The soiling mixture was left in the endoscope for2 hours. After 2 hrs, cleaning and rinsing was done according to theprotocol and as described in the previous examples. Harvesting theorganism or organic soil from the channels was done twice in sequence toensure a near perfect recovery. The cleaning composition as 0.7% Exilvain modified CS-19. For the air/water channel (A/W, ID 1.2 mm) thecleaning flow was 8 mL/min to a total of 250 mL, with 1,000 mL of rinse.For the SB channel (ID 3.7 mm) the cleaning flow was 12 mL/min to atotal of 400 mL, with 1,000 mL of rinse.

The results met cleaning specifications for bioburden. For bacteria,there was in one experiment a 4 log₁₀ reduction, and in another a near 4log₁₀ reduction.

This example confirms the effectiveness of cleaning according toembodiment of the invention in actual endoscopes. This example alsoshows that the technology applied to endoscope produces the same resultsas in the tube experiments described in the previous examples. Bothair/water and suction/biopsy channels are cleaned to very high levelswithout manual brushing or other manipulation. The data also show thatremoval of organic soil is extremely successful as was the case fortesting in Teflon tubes, as detailed in previous examples.

EXAMPLE 10 Enhanced Biofilm Cleaning

Under the conditions utilized (flow time, etc.), a Minute Fibrilcomposition did not fully remove BBF, but that composition with addedmicrocrystalline cellulose (NT-200 from FMC Corp.) did remove the BBF

BBF was formed in 3.7 mm diameter Teflon tube over 8 days according toprotocol as described elsewhere herein. The same tube was divided in twosections and was evaluated for BBF removal using two compositions (241and 242) under similar flow conditions as provided in the Table below.The suspending fluid was substantially similar to Modified CS-19.

Feed Composition I.D. Main Component Additive Run# (mm) Description Wt.% Description Wt. % 241 3.7 3:1 Epl/Ef 1.9 NT200 w fibers 2.00 242 3.73:1 Epl/Ef 1.9 none 0.00

Using the Anton Parr Rheometer Model 501, frequency sweeps showed thatComposition 241 has significantly high elastic properties [high G′ (2500Pa) and low G″ (500 Pa)] compared to Composition 241 where G′ and G″have low values between [(210 and 260 Pa)]. Amplitude sweeps (plots ofG′ and G″ versus shear stress) of the two compositions show that thecross over shear stress value of Composition 241 is about 45 Pa whilethat of Composition 242 was only about 13 Pa (FIG. 2). Since the crossover shear stress value is an indication of gel network strength (yieldshear stress), Composition 241 is much stronger gel network compared toComposition 242. The results of this Example indicate that networkstiffness as demonstrated G′ and G″ and their relative values as well asnetwork strength as indicated by yield shear stress are important indetermining the ability of the network to remove contaminants asexemplified here by BBF.

Not to be bound by theory, the stiffness (G′ or elastic modulus) andstrength of the gel network (yield shear stress) is usefully larger thanthat of the biofilm in order to achieve its more complete removal.Literature data indicate that G′ of biofilms can range from less than100 Pa to more than 2000 Pa (Stoodley et al., Structural deformation ofbacterial biofilms caused by short-term fluctuations in fluid shear: anin situ investigation of biofilm rheology,” Biotechnol Bioeng. 1999 Oct5; 65(1): 83-92). In embodiments, the network needs to be strong enough,having high yield shear stress, so that it can maintain sufficientelastic properties during flow in order achieve effective removal ofbiofilm as exemplified by BBF. Gel network compositions can be made tosatisfy such requirements according to embodiments of the invention.

EXAMPLE 11 Carbopol vs. Minute Fibrils on BBF

BBF was formed in a 1.37 mm Teflon tube over 8 days according to theprotocol as described elsewhere herein. Biofilm removal from the tubewas evaluated using two compositions: a) carbopol (Ultrez 10-Lubrizol)gel made at 0.17% by weight at pH which was adjusted by triethanol amineTEA) as recommended by Lubrizol, and b) Minute Fibril composition madeusing 1.9% by weight of 3:1 mixture of Epl and Ef in liquid vehiclesubstantially similar to CS-19. Both compositions had viscosities>9,000mPa·s. The carbopol gel exhibited higher yield shear stress values ascan judged by the no flow condition even when the vessel was invertedupside down. The operating parameters during cleaning were similar wherethe pressure drop was about 2.0 psi/linear foot and the volumetricvelocity was about 2 ml/minute. Cleaning effectiveness was measured bySEM, optical microscopy and visual examination.

In formulating carbopol gels the user must be aware that they aresensitive salt concentration and ionic strength as well as to pH more8.0. The structure of the polymer gel network can fall apart andtransform into lower viscosity polymer solution. In contrast, the MinuteFibrils gels of the invention can be formulated at a wide range of pH(from about 3.0 to about 12.0), ionic strength and salt concentrationand can accommodate surfactant and cleaning additives as in embodimentsof the invention.

The results showed that carbopol is an effective cleaning tool, butcomes up short in removing BBF. Only about 10% BBF removal was possiblewith the carbopol gel compared to about 100% removal with the MinuteFibril composition.

Not being bound by theory, polymer gels even if they possess highviscosity and if they have or do not have a yield shear stress cannotproduce mechanical forces at the wall sufficient remove BBF. The verythin nanofibrils of the carbopol gel seem to have low stiffness to causeBBF abrasion and erosion during flow. In contrast the fibers and fibrilsof the Minute fibril composition appear to have sufficient stiffness andare able to abrade, destroy and remove BBF as per embodiments of theinvention.

Numbered Embodiments

The invention can be further described with reference to the followingnumbered embodiments:

Embodiment A1: A cleaning composition comprising: (A) a carrier fluid;and (B) Minute Fibrils suspended in the carrier fluid, wherein thecomposition is protein cleaning effective.

Embodiment A2: The cleaning composition of an A Embodiment, wherein theMinute Fibrils are in a protein cleaning effective amount.

Embodiment A3: The cleaning composition of an A Embodiment, wherein theMinute Fibrils are in a BBF cleaning effective amount.

Embodiment A4: The cleaning composition of an A Embodiment, wherein thecomposition is BBF cleaning effective.

Embodiment A5: A cleaning composition of an A Embodiment, wherein thecomposition has one or more of the following features: (1) the MinuteFibrils are comprised of a major portion (50% or more by dry weight) ofa composition of Minute Fibrils with a first mean hydrodynamic size andanother portion of a composition of Minute Fibrils with a meanhydrodynamic size of 50% or less than the first mean hydrodynamic size;(2) solid particles or stiffening polymer effective to increase astorage modulus or yield shear stress of the composition; or (3) thecarrier fluid comprises propylene glycol or a glycol ether in amountseffective to increase cleaning of protein, carbohydrate, fat or biofilm;or (4) gel-forming polymers are added in amounts effective to increasethe yield shear stress of the composition; or (5) ionic polymer mixed toincrease the storage modulus or yield shear stress of the composition.

Embodiment A6: The cleaning composition of an A Embodiment, wherein thesolid particles or microcrystalline cellulose are effective to increasecleaning of BBF or protein.

Embodiment A7: The cleaning composition of an A Embodiment, wherein thesolid particles or microcrystalline cellulose are harder than a targetedcontaminant but less hard than the channel wall.

Embodiment A8: The cleaning composition of an A Embodiment, wherein atleast a portion of the solid particles or microcrystalline cellulose aremixed with the Minute Fibrils in such a way that SEM analysis would showa preference for exterior of flocs of the Minute Fibrils.

Embodiment A9: The cleaning composition of an A Embodiment, wherein thecarrier fluid comprises a surfactant.

Embodiment A10: The cleaning composition of an A Embodiment, wherein thew/w percentage of surfactant(s) is less than the w/w percentage ofMinute Fibrils.

Embodiment A 11: The cleaning composition of an A Embodiment, whereinthe composition has a yield shear stress of about 1 Pa to about 100 Pa.

Embodiment A12: The cleaning composition of an A Embodiment, wherein thecomposition has a yield shear stress of about 5 Pa to about 100 Pa.

Embodiment A13_alpha: The cleaning composition of an A Embodiment,wherein the Minute Fibrils are cellulosic.

Embodiment A13_beta: The cleaning composition of an A Embodiment,wherein the Minute Fibrils are synthetic.

Embodiment A14: The cleaning composition of an A Embodiment, wherein theMinute Fibrils comprise Type A fibrils of, and Type B fibrils, with SEMimages showing Type A fibrils connected to Type B fibrils.

Embodiment A15: The cleaning composition of an A Embodiment, wherein thecomposition displays shear thinning effective to facilitate emptying asix foot length of 3.2 mm ID channel at a pressure of about 30 p.s.i. orless.

Embodiment A16: The cleaning composition of an A Embodiment, wherein thecomposition displays a shear thinning when measured at a shear rate3.33/sec and 20/sec by a viscosity reduction of about 2-fold or more.

Embodiment A17: The cleaning composition of an A Embodiment, wherein theMinute Fibrils are comprised of a major portion (50% or more by dryweight) of a composition of Minute Fibrils with a first meanhydrodynamic size and another portion of a composition of Minute Fibrilswith a mean hydrodynamic size of 50% or less than the first meanhydrodynamic size.

Embodiment A18: The cleaning composition of an A Embodiment, whereinsolid particles are effective to increase a storage modulus or yieldshear stress of the composition

Embodiment A19: The cleaning composition of an A Embodiment, whereinstiffening polymer is effective to increase a storage modulus or yieldshear stress of the composition.

Embodiment A20: The cleaning composition of an A Embodiment, wherein thestiffening polymer is microcrystalline cellulose.

Embodiment A21: The cleaning composition of an A Embodiment, wherein thecarrier fluid comprises propylene glycol or a glycol ether.

Embodiment A22: The cleaning composition of an A Embodiment, whereingel-forming polymers are added in amounts effective to increase theyield shear stress of the composition.

Embodiment A23: The cleaning composition of an A Embodiment, whereinionic polymer is mixed to increase the storage modulus or yield shearstress of the composition.

Embodiment A24: The cleaning composition of an A Embodiment, whereinanionic polymer is mixed to increase the storage modulus or yield shearstress of the composition.

Embodiment A25: The cleaning composition of an A Embodiment, whereincationic polymer is mixed to increase the storage modulus or yield shearstress of the composition.

Embodiment B1: A kit comprising two or more cleaning compositions of anA Embodiment, one configured for use in a channel with an ID of about 1to about 2 mm, and one configured for use in a channel with an ID ofgreater than 2 mm to about 4 mm

Embodiment C1: The cleaning composition of an A Embodiment defining abody wash, wherein the body wash comprises antimicrobial agents thatconsist essentially of one or more essential oils.

Embodiment D1: A method of removing contaminants from a surfacecomprising:

providing a cleaning composition comprising a carrier fluid comprising,suspended in the carrier fluid, Minute Fibrils, or a gel-formingpolymer, or a mixture thereof; and

causing the cleaning composition to pass over surface with a bulk shearstress of about 1 Pa to about 100 Pa,

wherein the composition is protein cleaning effective.

Embodiment D2: The method of a D Embodiment, wherein the carrier fluidfurther comprises a surfactant.

Embodiment D3: The method of a D Embodiment, wherein the cleaningcomposition is that of any A Embodiment.

Embodiment D4: The method of a D Embodiment, wherein the method removesbiofilm.

Embodiment D5: The method of a D Embodiment, wherein the surface is in achannel of ID 4 mm or less, and wherein said biofilm is found 10 cm ormore from an opening for the channel.

Embodiment D6: The method of a D Embodiment, wherein the surface is in achannel of ID 2 mm or less.

Embodiment D7: The cleaning method of a D Embodiment, wherein the MinuteFibrils are in a protein cleaning effective amount.

Embodiment D8: The cleaning method of a D Embodiment, wherein the MinuteFibrils are in a BBF cleaning effective amount.

Embodiment D9: The cleaning method of a D Embodiment, wherein thecomposition is BBF cleaning effective.

Embodiment D10: The method of a D Embodiment, wherein the surface to becleaned is a narrow channel in a medical device, a surface of a medicaldevice, teeth, a surface of a precision cylinder, a cylinder-engagingsurface of a piston, a food preparation surface, skin (including for asurgical scrub), a surface of a gem, a glass surface (including opticalglass), a cutting blade surface, a prosthesis (including in vivo), awound, a filtration membrane, semiconductor material, a heat exchangertube, a pipe, a cutting tool, or a moldy portion of a building.

Embodiment E1: A cleaning device comprising: (I) a reservoir containinga cleaning composition comprising a carrier fluid comprising (a)suspended in the carrier fluid, Minute Fibrils, or a gel-formingpolymer, or a mixture thereof, wherein the composition is proteincleaning effective; and (II) a pump configured to draw cleaningcomposition from the reservoir and (a) into a channel to be cleaned ofdiameter of 10 mm or less and a length of 10 cm or more, or (b) onto aconfined space over an open surface to be cleaned, providing a bulkshear stress of 1 Pa or higher.

Embodiment E2: The cleaning device of a D Embodiment, wherein thesurface to be cleaned is in a channel.

Embodiment E3: The cleaning device of a D Embodiment, wherein thesurface to be cleaned is an open surface.

Embodiment E4: The cleaning device of a D Embodiment, wherein thecleaning composition is that of any A Embodiment.

Embodiment F1: A method of storing a medical device having one or morechannels of ID 6 mm or less, the method comprising: (A) filling thechannels with a sterile composition comprising a carrier fluidcomprising, suspended in the carrier fluid, Minute Fibrils, or agel-forming polymer, or a mixture thereof; and (B) after a period ofstorage, rinsing the sterile composition out such that the channel isfilled with a sterile fluid suitable for use while operating the medicaldevice.

Embodiment F2: The method of an F Embodiment, wherein the sterilecomposition comprises an antimicrobial or antibiotic.

Embodiment F3: The method of an F Embodiment, wherein the cleaningcomposition is that of any A Embodiment.

Incorporated Appendices

Attached to Provisional B (NOVA003P2) are the following Appendicessharing a common numbering (pages 1-291) that are incorporated herein byreference in their entirety:

TABLE 1 COMPOSITIONS AND METHODS FOR DECONTAMINATION, CLEANING,DISINFECTION, STORAGE AND STERILIZA- TION, p. 1 2 Various parameters, p.153 3 Elasticity and Stiffness, p. 165 4 Cleaning of external surfaces,p. 167 5 Endoscope Cleaning Apparatus, p. 177 6 Advanced CleaningEndoscope Tubes Using Plug Flow of Microfibrillated Cellulose, p. 204 7Biological testing results, p. 262 8 Prep Gel etc., p. 285 1COMPOSITIONS AND METHODS FOR DECONTAMINATION, CLEANING, DISINFECTION,STORAGE AND STERILIZA- TION, p. 1 2 Various parameters, p. 153 3Elasticity and Stiffness, p. 165 4 Cleaning of external surfaces, p. 1675 Endoscope Cleaning Apparatus, p. 177 6 Advanced Cleaning EndoscopeTubes Using Plug Flow of Microfibrillated Cellulose, p. 204 7 Biologicaltesting results, p. 262 8 Prep Gel etc., p. 285

This invention described herein is of a cleaning composition and methodsof forming and using the same. Although some embodiments have beendiscussed above, other implementations and applications are also withinthe scope of the following claims. Although the invention herein hasbeen described with reference to particular embodiments, it is to beunderstood that these embodiments are merely illustrative of theprinciples and applications of the present invention. It is therefore tobe understood that numerous modifications may be made to theillustrative embodiments and that other arrangements may be devisedwithout departing from the spirit and scope of the present invention asdefined by the following claims. More specifically, those of skill willrecognize that any embodiment described herein that those of skill wouldrecognize could advantageously have a sub-feature of another embodiment,is described as having that subfeature

Publications and references, including but not limited to patents andpatent applications, cited in this specification and in the priorityfilings (with their appendices) are herein incorporated by reference intheir entirety in the entire portion cited as if each individualpublication or reference were specifically and individually indicated tobe incorporated by reference herein as being fully set forth. Any patentapplication to which this application claims priority is alsoincorporated by reference herein in the manner described above forpublications and references.

What is claimed is:
 1. A cleaning composition comprising: a carrierfluid; and Minute Fibrils suspended in the carrier fluid, wherein thecomposition is protein cleaning effective.
 2. The cleaning compositionof claim 1, wherein the Minute Fibrils are in a protein cleaningeffective amount.
 3. The cleaning composition of claim 1, wherein theMinute Fibrils are in a BBF cleaning effective amount.
 4. The cleaningcomposition of claim 1, wherein the composition is BBF cleaningeffective.
 5. A cleaning composition of claim 1, wherein the compositionhas one or more of the following features: (1) the Minute Fibrils arecomprised of a major portion (50% or more by dry weight) of acomposition of Minute Fibrils with a first mean hydrodynamic size andanother portion of a composition of Minute Fibrils with a meanhydrodynamic size of 50% or less than the first mean hydrodynamic size;(2) solid particles or stiffening polymer effective to increase astorage modulus or yield shear stress of the composition; or (3) thecarrier fluid comprises propylene glycol or a glycol ether in amountseffective to increase cleaning of protein, carbohydrate, fat or biofilm;or (4) gel-forming polymers are added in amounts effective to increasethe yield shear stress of the composition; or (5) ionic polymer mixed toincrease the storage modulus or yield shear stress of the composition.6. The cleaning composition of claim 1, wherein the carrier fluidcomprises a surfactant.
 7. The cleaning composition of claim 6, whereinthe w/w percentage of surfactant(s) is less than the w/w percentage ofMinute Fibrils.
 8. The cleaning composition of claim 1, wherein thecomposition has a yield shear stress of about 5 Pa to about 100 Pa. 9.The cleaning composition of claim 1, wherein the composition displays ashear thinning when measured at a shear rate 3.33/sec and 20/sec by aviscosity reduction of about 2-fold or more.
 10. A kit comprising two ormore cleaning compositions of claim 1, one configured for use in achannel with an ID of about 1 to about 2 mm, and one configured for usein a channel with an ID of greater than 2 mm to about 4 mm.
 11. Thecleaning composition of claim 1 defining a body wash, wherein the bodywash comprises antimicrobial agents that consist essentially of one ormore essential oils.
 12. A method of removing contaminants from asurface comprising: providing a cleaning composition comprising acarrier fluid comprising, suspended in the carrier fluid, MinuteFibrils, or a gel-forming polymer, or a mixture thereof; and causing thecleaning composition to pass over surface with a bulk shear stress ofabout 1 Pa to about 100 Pa, wherein the composition is protein cleaningeffective.
 13. The method of claim 12, wherein the carrier fluid furthercomprises a surfactant.
 14. The method of claim 12, wherein the methodremoves biofilm
 15. The method of claim 14, wherein the surface is in achannel of ID 4 mm or less, and wherein said biofilm is found 10 cm ormore from an opening for the channel
 16. The method of claim 15, whereinthe surface is in a channel of ID 2 mm or less.
 17. The cleaning methodof claim 12, wherein the Minute Fibrils are in a protein cleaningeffective amount.
 18. The cleaning method of claim 12, wherein theMinute Fibrils are in a BBF cleaning effective amount.
 19. The cleaningmethod of claim 12, wherein the composition is BBF cleaning effective.20. The cleaning method of claim 12, wherein the surface to be cleanedis a narrow channel in a medical device, a surface of a medical device,teeth, a surface of a precision cylinder, a cylinder-engaging surface ofa piston, a food preparation surface, skin, a surface of a gem, a glasssurface, a cutting blade surface, a prosthesis, a wound, a filtrationmembrane, semiconductor material, a heat exchanger tube, a pipe, acutting tool, or a moldy portion of a building.
 21. A cleaning devicecomprising: a reservoir containing a cleaning composition comprising acarrier fluid comprising (a) suspended in the carrier fluid, MinuteFibrils, or a gel-forming polymer, or a mixture thereof, wherein thecomposition is protein cleaning effective; and a pump configured to drawcleaning composition from the reservoir and (a) into a channel to becleaned of diameter of 10 mm or less and a length of 10 cm or more, or(b) onto a confined space over an open surface to be cleaned, providinga bulk shear stress of 1 Pa or higher.
 22. A method of storing a medicaldevice having one or more channels of ID 6 mm or less, the methodcomprising: filling the channels with a sterile composition comprising acarrier fluid comprising, suspended in the carrier fluid, MinuteFibrils, or a gel-forming polymer, or a mixture thereof; and after aperiod of storage, rinsing the sterile composition out such that thechannel is filled with a sterile fluid suitable for use while operatingthe medical device.